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1

Browall, Sarah, Erik Backhaus, Pontus Naucler, et al. "Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types." European Respiratory Journal 44, no. 6 (2014): 1646–57. http://dx.doi.org/10.1183/09031936.00080814.

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Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored.Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children.The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality.PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.
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2

Gladstone, R. A., J. M. Jefferies, S. N. Faust, and S. C. Clarke. "Continued control of pneumococcal disease in the UK – the impact of vaccination." Journal of Medical Microbiology 60, no. 1 (2011): 1–8. http://dx.doi.org/10.1099/jmm.0.020016-0.

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Streptococcus pneumoniae, also known as the pneumococcus, is an important cause of morbidity and mortality in the developed and developing world. Pneumococcal conjugate vaccines were first introduced for routine use in the USA in 2000, although the seven-valent pneumococcal conjugate vaccine (PCV7) was not introduced into the UK's routine childhood immunization programme until September 2006. After its introduction, a marked decrease in the incidence of pneumococcal disease was observed, both in the vaccinated and unvaccinated UK populations. However, pneumococci are highly diverse and serotype prevalence is dynamic. Conversely, PCV7 targets only a limited number of capsular types, which appears to confer a limited lifespan to the observed beneficial effects. Shifts in serotype distribution have been detected for both non-invasive and invasive disease reported since PCV7 introduction, both in the UK and elsewhere. The pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix; GlaxoSmithKline) and 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13; Pfizer) have been newly licensed. The potential coverage of the 10- and 13-valent conjugate vaccines has also altered alongside serotype shifts. Nonetheless, the mechanism of how PCV7 has influenced serotype shift is not clear-cut as the epidemiology of serotype prevalence is complex. Other factors also influence prevalence and incidence of pneumococcal carriage and disease, such as pneumococcal diversity, levels of antibiotic use and the presence of risk groups. Continued surveillance and identification of factors influencing serotype distribution are essential to allow rational vaccine design, implementation and continued effective control of pneumococcal disease.
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3

Greenwood, Brian. "The epidemiology of pneumococcal infection in children in the developing world." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354, no. 1384 (1999): 777–85. http://dx.doi.org/10.1098/rstb.1999.0430.

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Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100 000–500 000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio–economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing counties. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide–protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.
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4

McIntyre, Peter. "Epidemiology and prevention of pneumococcal disease." Communicable Diseases Intelligence 21 (February 20, 1997): 41–46. https://doi.org/10.33321/cdi.1997.21.9.

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There are comparatively little data on the incidence and morbidity from pneumococcal disease in Australia and elsewhere. Available data suggest that the overall incidence of invasive pneumococcal disease in Australia is comparable with similar populations. Very high rates are reported in Central Australian Aborigines, similar to invasive Haemophilus influenzae type b (Hib) disease. Disease incidence is probably greatly underestimated by case ascertainment from sterile site isolates alone. New diagnostic methods, such as serology to detect components of the pneumococcal cell wall, promise to significantly enhance detection of pneumococci as a cause of pneumonia, especially in childhood, but are epidemiologic rather than clinical tools. Resistance to penicillin and other antibiotics is an increasing problem worldwide, promoted by excessive antibiotic use, especially in children. This has focused attention on vaccine prevention. Fortunately, antibiotic-resistant pneumococci appear to belong to a limited range of serotypes, those commonly colonising children, in all areas so far studied. If conjugate pneumococcal vaccines prove to eradicate carriage, in a similar fashion to conjugate Hib vaccines, vaccination may be the major weapon against the spread of antibiotic-resistant pneumococcal infection. Conjugate pneumococcal vaccines are now in large scale efficacy trials, with outcomes of bacteraemia (California) and otitis media (Finland). Results of these trials are eagerly awaited. Comm Dis Intell 1997;21:41-46.
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5

Dagan, Ronald N. "Antibiotic resistance and the potential impact of pneumococcal conjugate vaccines." Communicable Diseases Intelligence 27 (May 30, 2003): S135—S142. https://doi.org/10.33321/cdi.2003.27.37.

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Streptococcus pneumoniae is a major cause of morbidity and mortality in young children throughout the world, causing both invasive (meningitis, bacteraemia) and non-invasive (pneumonia, acute otitis media, sinusitis) infections. Over the past few decades, the global emergence of antibiotic-resistant pneumococcal strains has complicated disease management. Thus, healthcare practitioners have begun to place more emphasis on the judicious use of antibiotics and prevention of disease through routine immunisation. Researchers have developed several pneumococcal conjugate vaccines, which due to their technology, are effective in infants and young children. Currently, one 7-valent pneumococcal conjugate vaccine (PNCRM7; Prevenar®, Wyeth) is available in various parts of the world and has demonstrated excellent efficacy against vaccine-type invasive disease and efficacy against pneumonia and otitis media caused by the serotypes included in the vaccine. Furthermore, there is evidence suggesting that the use of these conjugate vaccines will reduce the need for antibiotics and the subsequent spread of antibiotic-resistant pneumococci. Ultimately, when routine pneumococcal conjugate vaccination of infants and young children is accompanied by supportive education and active disease surveillance as well as judicious use of antibiotics, there should be a favourable impact on pneumococcal disease incidence in and beyond the vaccinated population. Commun Dis Intell 2003;27 Suppl:S134-S142.
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6

Gruber, I. M., O. M. Kukina, N. B. Egorova,, and O. V. Zhigunova. "Different Technologies for Obtaining Pneumococcal Immunogens." Epidemiology and Vaccinal Prevention 20, no. 1 (2021): 76–91. http://dx.doi.org/10.31631/2073-3046-2021-20-1-76-91.

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Relevance. The worldwide use of pneumococcal vaccines, in particular conjugated vaccines (PCV), has led to a significant reduction in the incidence of invasive pneumococcal diseases in both vaccinated children and unvaccinated people of all ages. However, "non-vaccine" serotypes and capsule-free (non-typed) strains have become the main causes of pneumococcal disease, as with carriage, with an increase in antibiotic resistance. This requires new approaches in the development of vaccines that can lead to serotype-independent protection, especially in children, the elderly and immunocompromised people. The pneumococcal vaccine should protect against a wide range of serotypes, induce mucosal and systemic immunity, and reduce primary nasal colonization, as well as invasive forms. Aim. The review is devoted to the analysis of experimental development of innovative vaccines based on protective protein antigens (PPV), including in combination with capsular polysaccharides, using adjuvants or antigen delivery systems, as well as inactivated whole cell preparations (WCV) and live attenuated vaccines. Particular attention is paid to the methods of mucosal immunization, taking into account the tropism of pneumococcus in relation to the mucous membranes of the upper and lower respiratory tract. Conclusion. At this stage, the most developed and promising are drugs based on bacterial lysates (PWCV) and protective protein antigens (PspA, dPly), as well as these antigens mixed with adjuvants, and, possibly, with some etiologically most significant capsular polysaccharides.
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7

Thong, Bernard Yu-Hor, Ruby Pawankar, Hae-Sim Park, and Amir Hamzah Abdul Latiff. "Evaluating immune responses to pneumococcal vaccines." Asia Pacific Allergy 13, no. 3 (2023): 127–31. http://dx.doi.org/10.5415/apallergy.0000000000000114.

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Streptococcus pneumoniae (pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe diseases including bacteremia, pneumonia, and invasive pneumococcal disease (IPD) (eg, meningitis, septic arthritis, and endocarditis). Pneumococcal vaccines were first developed in the 1970s as capsular pneumococcal polysaccharide vaccines, which were T-cell independent and hence lacked immunologic memory. Subsequently in the year 2000, pneumococcal conjugate vaccines (PCV) conjugated to a protein to increase immunogenicity were developed and made commercially available. The increasing number of pneumococcal serotypes identified and the expanding pipeline of PCV vaccines with improved immunogenicity have significantly reduced the morbidity and mortality associated with IPD in high-risk patients. Pneumococcal vaccines also play an important role in the diagnosis and immunophenotyping of children and adults with inborn errors of immunity (IEI) given the increasing diversity/heterogeneity of IEI presenting with primary and/or specific antibody deficiency. Other than the quantitation of serotype levels in routine clinical care, other measurements of immune response including the functional activity of antibodies, antibody avidity, cell-mediated immunity, and immunological memory remain limited to clinical trials during vaccine development.
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8

Ignatova, G. L., V. N. Antonov, M. P. Kostinov, and A. D. Protasov. "Individual protection and population effect – two sides of one medal." Medical Council, no. 15 (October 12, 2018): 102–9. http://dx.doi.org/10.21518/2079-701x-2018-15-102-109.

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The studies of the serotype composition of pneumococci in various countries indicate that over 80% of the most severe invasive diseases are caused by 20 serotypes, and 13 serotypes cause 70–75% of diseases globally [3]. The vaccination of the population is the main way to reduce the incidence of both invasive and non-invasive pneumococcal infections. With evidence of the safety and efficacy of pneumococcal conjugate vaccines, WHO and UNCF consider it necessary to include these vaccines for children in the national immunization programs around the world.
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9

Kiran, Dr G. Usha, B. Aasritha, B. Jhansi lakshmi, J. Lulika Kumari, B. Sujitha, and G. Thanmaya swathi. "Pneumococcal Vacine: Overall View." International Journal for Research in Applied Science and Engineering Technology 12, no. 8 (2024): 641–47. http://dx.doi.org/10.22214/ijraset.2024.63970.

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Abstract: Streptococcus pneumonia is a leading cause of invasive pneumococcal disease (IPD), resulting in significant morbidity and mortality worldwide. Pneumococcal vaccines have been instrumental in preventing IPD, particularly in vulnerable populations such as children , older adults and those with compromised immune systems.This article reviews current landscape of pneumococcal vaccine , including the available conjugate and polysaccharide vaccines, their immunogencity,efficacy and safety profiles.We discuss the impact of pneumococcal vaccination on IPD incidence,stereo type distrubuttion and anti biotic resistance.Additionally, we explore emerging vaccine technologies,such as protein based and mRNA vaccines,and their potential to enhance protection against pneumococcal disease.The article concludes with a discussion on the future directions for pneumococcal vaccine development,including the need for broader protection , improved immunogencity and increased access to vaccines in low- resource settings.
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10

Daniels, Calvin C., P. David Rogers, and Chasity M. Shelton. "A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens." Journal of Pediatric Pharmacology and Therapeutics 21, no. 1 (2016): 27–35. http://dx.doi.org/10.5863/1551-6776-21.1.27.

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This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines.
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11

Patel, Sweta M., Yazdani B. Shaik-Dasthagirisaheb, Morgan Congdon, et al. "Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine." PLOS ONE 17, no. 1 (2022): e0262225. http://dx.doi.org/10.1371/journal.pone.0262225.

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Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.
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12

Morais, Texeira, and Suarez. "Next-Generation Whole-Cell Pneumococcal Vaccine." Vaccines 7, no. 4 (2019): 151. http://dx.doi.org/10.3390/vaccines7040151.

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Streptococcus pneumoniae remains a major public health hazard. Although Pneumococcal Conjugate Vaccines (PCVs) are available and have significantly reduced the rate of invasive pneumococcal diseases, there is still a need for new vaccines with unlimited serotype coverage, long-lasting protection, and lower cost to be developed. One of the most promising candidates is the Whole-Cell Pneumococcal Vaccine (WCV). The new generation of whole-cell vaccines is based on an unencapsulated serotype that allows the expression of many bacterial antigens at a lower cost than a recombinant vaccine. These vaccines have been extensively studied, are currently in human trial phase 1/2, and seem to be the best treatment choice for pneumococcal diseases, especially for developing countries.
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13

Clarke, Stuart C., Johanna M. C. Jefferies, Andrew J. Smith, Jim McMenamin, Timothy J. Mitchell, and Giles F. S. Edwards. "Pneumococci causing invasive disease in children prior to the introduction of pneumococcal conjugate vaccine in Scotland." Journal of Medical Microbiology 55, no. 8 (2006): 1079–84. http://dx.doi.org/10.1099/jmm.0.46550-0.

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This study aimed to determine the serotypes and sequence types (STs) of pneumococci causing paediatric invasive disease in Scotland prior to the introduction of pneumococcal conjugate vaccines (PCVs). All invasive pneumococci isolated between 2000 and 2004 from children aged less than 5 years in Scotland were used. The isolates were characterized by serotyping and multi-locus sequence typing. Two hundred and seventeen pneumococci were characterized into 22 different serogroups/types, the most common, in rank order, being 14, 19F, 6B, 18C, 23F, 9V, 4, 1, 19A and 6A. They were further genotyped into 77 different STs, the three most common being 9, 162 and 176. Common serotypes possessed multiple STs, but pneumococci of a particular clone were mostly associated with a particular serotype. The seven most common serotypes are included in the 7-valent polysaccharide conjugate vaccine (PCV7). Serotype coverage for PCV7 was 76.5 % in those aged less than 5 years but increased to 88.9 % for those aged 1 year. The introduction of PCV7 into the childhood immunization schedule would reduce the burden of pneumococcal disease in children, although continued surveillance of invasive pneumococcal disease will be required before, during and after the introduction of PCVs.
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14

KYAW, M. H., S. CLARKE, G. F. S. EDWARDS, I. G. JONES, and H. CAMPBELL. "Serotypes/groups distribution and antimicrobial resistance of invasive pneumococcal isolates: implications for vaccine strategies." Epidemiology and Infection 125, no. 3 (2000): 561–72. http://dx.doi.org/10.1017/s0950268800004787.

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Based on the invasive pneumococcal isolates referred to reference laboratories in Scotland in 1988–99, we identified the distribution of serotypes/groups and their antimicrobial resistance patterns in order to evaluate the coverage of polysaccharide and the new pneumococcal conjugate vaccines. A total of 5659 invasive isolates were included. Of these, 5124 (90·5%) were blood isolates, 308 (5·5%) were CSF isolates, 143 (2·5%) were blood and CSF and 84 (1·5%) were other normally sterile isolates. The most prevalent 11 serotypes/groups were 14, 9, 19, 6, 23, 1, 3, 4, 7, 8 and 18, in numerical order. These accounted for 84% of total serotypes/groups.The serotypes/groups included in the 23 and 14-valent polysaccharide vaccines accounted for 96% and 88% of all isolates. Both vaccines accounted for 98% of penicillin non-susceptible and 100% of erythromycin non-susceptible isolates. The 7, 9, and 11-valent conjugate vaccines covered 61, 68 and 80% of invasive isolates respectively. The coverage of these vaccines was substantially higher in youngest age group with 84, 86 and 93% of invasive isolates in children < 2 years included in the 7, 9 and 11-valent conjugate vaccines compared with 58, 64 and 77% in adults [ges ] 65 years of age.The serotype/group distribution of invasive isolates in Scotland varied from year to year over the period 1993–9. The coverage of the 23-valent vaccine remained above 95% in each year but the coverage of the 7, 9 and 11-valent conjugate vaccines showed more marked fluctuation with coverage as low as 53, 60 and 75% in some years. Continued surveillance of invasive pneumococcal isolates is required to inform the development of appropriate vaccine strategies to prevent pneumococcal disease in Scotland.
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15

Jakobsen, Håvard, Eiríkur Saeland, Sveinbjörn Gizurarson, Dominique Schulz, and Ingileif Jónsdóttir. "Intranasal Immunization with Pneumococcal Polysaccharide Conjugate Vaccines Protects Mice against Invasive Pneumococcal Infections." Infection and Immunity 67, no. 8 (1999): 4128–33. http://dx.doi.org/10.1128/iai.67.8.4128-4133.1999.

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ABSTRACT Host defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i.n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections.
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Rafei, Rayane, Mazen Zaylaa, Mohamad Diab, et al. "Nasopharyngeal Carriage, Antimicrobial Resistance, and Serotype Distribution of Streptococcus pneumoniae in Children Under Five in Lebanon: Baseline Data Prior to PCV13 Introduction." Antibiotics 14, no. 2 (2025): 168. https://doi.org/10.3390/antibiotics14020168.

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Background: The nasopharyngeal carriage of Streptococcus pneumoniae can be the source of transmission between humans and the starting step towards invasive pneumococcal diseases. Data on the carriage of pneumococci in children before and after the pneumococcal conjugate vaccines (PCV) integration in a country are essential for monitoring any change in pneumococcal carriage serotypes and their antimicrobial-resistance profiles. Methods: We investigated the epidemiology of S. pneumoniae carriage among children younger than five years old in Tripoli, Lebanon, in 2016, the same year of integration of PCV13 in the country’s Expanded Program on Immunization. Results: Of 104 participating children, 57 (54.8%) gave a positive culture for S. pneumoniae. Antimicrobial susceptibility testing revealed that 26.3% of isolates were multidrug-resistant. Resistance was detected mainly against oxacillin (77.2%), tetracycline (29.8%), erythromycin (22.8%), trimethoprim-sulfamethoxazole (22.8%), clindamycin (19.3%), minocycline (19.3%), and teicoplanin (1.8%). Serotyping analysis identified 14 distinct serotypes, with only 31.3% and 50% of isolates corresponding to vaccine serotypes covered by PCV13 and PCV20, respectively. The most common serotypes were 11A, 19F, 23A, and those of serogroup 24 (Sg24) accounted for 37.5% of the serotyped isolates. Conclusions: Our findings have revealed the circulation of a pool of pneumococci isolates with high levels of antibiotic resistance and different degrees of likelihood of causing invasive diseases in children under five years old in Tripoli in 2016. The overall limited PCV13 vaccine coverage in this study highlighted the need for vaccines with greater coverage in the immunization programs in Lebanon. Longitudinal national studies investigating the carriage of pneumococci in children are required to further assess the impact of the PCV vaccine on pneumococci carriage in children and steer new vaccine development.
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Xu, Xiuyu, Hong Wang, Yusi Liu, et al. "Mucosal Immunization with the Live Attenuated Vaccine SPY1 Induces Humoral and Th2-Th17-Regulatory T Cell Cellular Immunity and Protects against Pneumococcal Infection." Infection and Immunity 83, no. 1 (2014): 90–100. http://dx.doi.org/10.1128/iai.02334-14.

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Mucosal immunization with attenuated vaccine can protect against pneumococcal invasion infection, but the mechanism was unknown. Our study found that mucosal delivery with the live attenuated SPY1 vaccine strain can confer T cell- and B cell-dependent protection against pneumococcal colonization and invasive infection; yet it is still unclear which cell subsets contribute to the protection, and their roles in pneumococcal colonization and invasion remain elusive. Adoptive transfer of anti-SPY1 antibody conferred protection to naive μMT mice, and immune T cells were indispensable to protection examined in nude mice. A critical role of interleukin 17A (IL-17A) in colonization was demonstrated in mice lacking IL-17A, and a vaccine-specific Th2 immune subset was necessary for systemic protection. Of note, we found that SPY1 could stimulate an immunoregulatory response and that SPY1-elicited regulatory T cells participated in protection against colonization and lethal infection. The data presented here aid our understanding of how live attenuated strains are able to function as effective vaccines and may contribute to a more comprehensive evaluation of live vaccines and other mucosal vaccines.
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Parry, Christopher M., Nguyen Minh Duong, Jiaji Zhou, et al. "Emergence in Vietnam of Streptococcus pneumoniae Resistant to Multiple Antimicrobial Agents as a Result of Dissemination of the Multiresistant Spain23F-1 Clone." Antimicrobial Agents and Chemotherapy 46, no. 11 (2002): 3512–17. http://dx.doi.org/10.1128/aac.46.11.3512-3517.2002.

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ABSTRACT Surveillance for Streptococcus pneumoniae resistant to penicillin and other antimicrobial agents is necessary to define the optimal empirical antibiotic therapy for meningitis in resource-poor countries such as Vietnam. The clinical and microbiological features of 100 patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, Vietnam, between 1993 and 2002 with invasive pneumococcal disease were studied. A penicillin-nonsusceptible pneumococcus (MIC, ≥0.1 μg/ml) was isolated from the blood or cerebrospinal fluid of 8% of patients (2 of 24) between 1993 and 1995 but 56% (20 of 36) during 1999 to 2002 (P < 0.0001). Pneumococcal isolates resistant to penicillin (MIC, ≥2.0 μg/ml) increased from 0% (0 of 24) to 28% (10 of 36) (P = 0.002). Only one isolate was ceftriaxone resistant (MIC, 2.0 μg/ml). Penicillin-nonsusceptible pneumococci were isolated from 78% of children younger than 15 years (28 of 36) compared with 25% of adults (16 of 64) (P = 0.0001). Isolation of a penicillin-nonsusceptible pneumococcus in adults with meningitis was independently associated with referral from another hospital (P = 0.005) and previous antibiotic therapy (P = 0.025). Multilocus sequence typing showed that 86% of the invasive penicillin-resistant pneumococcus isolates tested (12 of 14) were of the Spain23F-1 clone. The serotypes of >95% of the penicillin-nonsusceptible pneumococci were included in the currently available pneumococcal vaccines. Our findings point to the recent introduction and spread of the Spain23F-1 clone of penicillin-resistant pneumococci in Vietnam. Simple clinical predictors can be used to guide empirical antibiotic therapy of meningitis. Pneumococcal vaccination may help to control this problem.
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Ozisik, Lale. "The New Era of Pneumococcal Vaccination in Adults: What Is Next?" Vaccines 13, no. 5 (2025): 498. https://doi.org/10.3390/vaccines13050498.

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Streptococcus pneumoniae remains the leading cause of community-acquired pneumonia in adults and bacterial meningitis in children worldwide. In addition to pneumonia, invasive pneumococcal diseases (IPDs), such as bacteremia and meningitis, pose a significant burden, particularly among older adults and individuals with underlying comorbidities. These diseases lead to substantial morbidity and mortality. Pneumococcal vaccination has been a cornerstone of disease prevention, reducing incidence and antimicrobial resistance. Recent advances in understanding S. pneumoniae epidemiology, genomic diversity, and the real-world impact of conjugate vaccines have driven the development and licensure of new-generation pneumococcal vaccines with expanded serotype coverage. Introducing 15-valent (PCV15), 20-valent (PCV20), and 21-valent (PCV21) conjugate vaccines has reshaped pneumococcal immunization strategies, particularly in adults, replacing previous sequential vaccine recommendations in many settings. In parallel, emerging epidemiological data and shifts in pneumococcal serotype distribution continue to influence vaccine policy decisions and immunization guidelines worldwide. In light of these advancements, adult pneumococcal vaccination recommendations continuously evolve to enhance protection in high-risk populations and optimize long-term immunity. This review provides an updated overview of the pneumococcal disease burden, the evolution of pneumococcal vaccines, and the latest immunization strategies in an expanding vaccine landscape. Additionally, we discuss future directions in pneumococcal vaccine development and the potential impact of novel vaccination approaches on public health outcomes.
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20

Denham, B. C., and S. C. Clarke. "Serotype incidence and antibiotic susceptibility of Streptococcus pneumoniae causing invasive disease in Scotland, 1999–2002." Journal of Medical Microbiology 54, no. 4 (2005): 327–31. http://dx.doi.org/10.1099/jmm.0.45718-0.

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Pneumococcal disease remains an important cause of invasive and non-invasive disease in Scotland and elsewhere. The Scottish Meningococcus and Pneumococcus Reference Laboratory receives isolates of Streptococcus pneumoniae from diagnostic laboratories around Scotland. Here, the serogroups/types and antibiotic-susceptibility patterns of invasive isolates received between 1999 and 2002 are described. There were a total of 1741 invasive isolates received, the most common serogroups/types being 14 (19.8 %), 9 (10.2 %), 6 (8.3 %), 19 (7.9 %), 23 (7.9 %), 4 (6.5 %), 8 (6.4 %), 3 (5.7 %), 1 (3.8 %), 7 (3.8 %) and 18 (3.4 %). Importantly, serotypes 7 and 8 are not represented in the 7-, 9- and 11-valent pneumococcal conjugate polysaccharide vaccines. There were 67 (3.8 %) isolates considered penicillin non-susceptible, although no penicillin resistance (MIC ⩾ 0.002 mg ml−1) was recorded. One hundred and ninety-four (11.1 %) isolates, predominantly of serotype 14, were resistant to erythromycin, and 12 (0.7 %) were resistant to ciprofloxacin. This information provides an important dataset that will prove essential prior to and during the implementation of pneumococcal conjugate vaccines in the UK.
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Forrest, Jill M., Peter B. McIntyre, and Margaret A. Burgess. "Pneumococcal disease in Australia: Summary of the Pneumococcal Disease in Australia: Epidemiology, Surveillance and Immunisation Workshop." Communicable Diseases Intelligence 24 (April 30, 2000): 89–92. https://doi.org/10.33321/cdi.2000.24.13.

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The proceedings of the Pneumococcal Disease in Australia Workshop, held on 26-27 March 1999 are presented in this report. The world-wide epidemiology of the pneumococcus, with its predilection for the very young and the very old, differs between the developing and the developed world, and between indigenous and non-indigenous populations. Sources of data on pneumococcal disease in each of the Australian States, clinical aspects of invasive and non-invasive disease, and the role of the public health laboratory in surveillance of serotypes and antimicrobial sensitivity, both nationally and over time, were discussed at the Workshop. Polysaccharide pneumococcal vaccines are recommended for those over 65 years of age and for at-risk groups, but are supplied free of charge only in Victoria and for indigenous Australians over 50 years of age. Children will require conjugate vaccines, which are likely to be licensed in the United States of America early in 2000. In Australia indigenous children, especially in rural areas, will be the priority group for conjugate vaccines. Commun Dis Intell 2000;24:89-92.
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22

Roberts, HJ, and WS Lim. "Influenza and pneumococcal vaccination: an update." Journal of the Royal College of Physicians of Edinburgh 37, no. 3 (2007): 228–31. https://doi.org/10.1177/1478271520073703013.

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Influenza and Streptococcus pneumoniae cause considerable morbidity and mortality. Excess deaths in the UK per year from influenza have been between 2,000 and 4,000 in recent years. There are over 5,000 cases of invasive pneumococcal disease in the UK per annum. Vaccination was introduced to the UK in the eighteenth century. Since then, there have been major advances in the development and administration of vaccines. The use of hens’ eggs for viral growth meant that influenza vaccination became more widely available, and the recognition of different serotypes of pneumococcus led to increased effectiveness of immunisation. Recent developments have led to a conjugate pneumococcal vaccine which is effective in children and has had dramatic effects on the incidence of invasive disease in the US. It has recently been introduced into the childhood immunisation programme in the UK. This article gives a background to the development of influenza and pneumococcal vaccination, and an update on recent advances and recommendations.
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Korona-Glowniak, Izabela, and Anna Malm. "Characteristics ofStreptococcus pneumoniaeStrains Colonizing Upper Respiratory Tract of Healthy Preschool Children in Poland." Scientific World Journal 2012 (2012): 1–10. http://dx.doi.org/10.1100/2012/732901.

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Antibiotic resistant and invasive pneumococci may spread temporally and locally in day care centers (DCCs). We examined 267 children attending four DCCs located in the same city and 70 children staying at home in three seasons (autumn, winter, and spring) to determine prevalence, serotype distribution, antibiotic resistance patterns, and transmission of pneumococcal strains colonizing upper respiratory tract of healthy children without antipneumococcal vaccination. By pheno- and genotyping, we determined clonality of pneumococci, including drug-resistant strains. The average carriage of pneumococci in three seasons was 38.2%. 73.4% and 80.4% of the isolates belonged to serotypes present in 10- and 13-valent conjugate vaccine, respectively. Among the pneumococcal strains, 33.3% were susceptible to all antimicrobial tested and 39.2% had decreased susceptibility to penicillin. Multidrug resistance was common (35.7%); 97.5% of drug-resistant isolates represented serotypes included to 10- and 13-valent conjugate vaccine. According to BOX-PCR, clonality definitely was observed only in case of serotype 14. Multivariate analysis determined DCC attendance as strongly related to pneumococcal colonization in all three seasons, but important seasonal differences were demonstrated. In children attending DCCs, we observed dynamic turnover of pneumococcal strains, especially penicillin nonsusceptible and multidrug resistant, which were mostly distributed among serotypes included to available pneumococcal conjugate vaccines.
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Deng, James Z., Zhifeng Chen, James Small, et al. "Identification and Quantification of a Pneumococcal Cell Wall Polysaccharide by Antibody-Enhanced Chromatography Assay." Vaccines 12, no. 5 (2024): 469. http://dx.doi.org/10.3390/vaccines12050469.

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Multivalent pneumococcal vaccines have been developed successfully to combat invasive pneumococcal diseases (IPD) and reduce the associated healthcare burden. These vaccines employ pneumococcal capsular polysaccharides (PnPs), either conjugated or unconjugated, as antigens to provide serotype-specific protection. Pneumococcal capsular polysaccharides used for vaccine often contain residual levels of cell wall polysaccharides (C-Ps), which can generate a non-serotype specific immune response and complicate the desired serotype-specific immunity. Therefore, the C-P level in a pneumococcal vaccine needs to be controlled in the vaccine process and the anti C-P responses need to be dialed out in clinical assays. Currently, two types of cell-wall polysaccharide structures have been identified: a mono-phosphocholine substituted cell-wall polysaccharide C-Ps1 and a di-phosphocholine substituted C-Ps2 structure. In our effort to develop a next-generation novel pneumococcal conjugate vaccine (PCV), we have generated a monoclonal antibody (mAb) specific to cell-wall polysaccharide C-Ps2 structure. An antibody-enhanced HPLC assay (AE-HPLC) has been established for serotype-specific quantification of pneumococcal polysaccharides in our lab. With the new anti C-Ps2 mAb, we herein extend the AE-HPLC assay to the quantification and identification of C-Ps2 species in pneumococcal polysaccharides used for vaccines.
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Marks, Jessie, Guru V. Bhoojhawon, Katherine D. Patrick, and Kelly E. Wood. "Emergence of Meningitis Caused by Nonvaccine Serotypes of Pneumococcus in Rural United States." Case Reports in Pediatrics 2020 (November 27, 2020): 1–3. http://dx.doi.org/10.1155/2020/2372843.

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Pneumococcal conjugate vaccines have decreased the rates of invasive pneumococcal disease (IPD) in children. Since vaccine introduction, however, rates of infection due to nonvaccine Streptococcus pneumoniae serotypes have increased. We now describe 3 meningitis cases due to the nonvaccine serotypes 35B and 11A from rural United States.
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Kim, Lindsay, Lesley McGee, Sara Tomczyk, and Bernard Beall. "Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective." Clinical Microbiology Reviews 29, no. 3 (2016): 525–52. http://dx.doi.org/10.1128/cmr.00058-15.

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SUMMARYStreptococcus pneumoniaeinflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand.
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Rao, Chythra R., Veena G. Kamath, Anuradha Nadda, et al. "IAPSM’s Position Paper on Pneumococcal Vaccine (PCV) for Adult Immunization in India." Indian Journal of Community Medicine 49, Suppl 2 (2024): S132—S138. https://doi.org/10.4103/ijcm.ijcm_739_24.

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Pneumococcal infection among adults is associated with invasive disease and poor outcomes. Pneumococcal vaccine (PCV) introduction has significantly reduced disease burden, invasive disease and reduced the rates of antimicrobial resistance. Of the various vaccines licensed, PCV 13 and PPSV 23 are available for use in India. Pneumococcal vaccination is suggested for people aged 19–64 years with immunosuppression, chronic cardiac, lung and hepatic disease, impaired splenic function, uncontrolled diabetes mellitus, current smokers, and those abusing alcohol. It is recommended that people >65 years of age are vaccinated with PPSV23. The suggested regimen is to administer PCV13 followed by PPSV23 after one year. The vaccines have minimal side effects and tolerated well. Data on vaccine effectiveness from Indian studies is limited. Hence, documenting population demographics with surveillance on serotype specific pneumococcal disease burden in adults is needed. Following this, studies on safety, immunogenicity, and cost-effectiveness of the available vaccines need to be designed and implemented. It is suggested that in the initial phase, PCV needs to be made available for high-risk population followed by vaccination roll-out for adult population of India.
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Morton, Ben, Kondwani Jambo, Tarsizio Chikaonda, et al. "The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol." Wellcome Open Research 6 (June 16, 2022): 240. http://dx.doi.org/10.12688/wellcomeopenres.17172.2.

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Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation. For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi. This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with S. pneumoniae serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population. Trial Registration: Pan African Clinical Trial Registry (REF: PACTR202008503507113)
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29

Morton, Ben, Kondwani Jambo, Tarsizio Chikaonda, et al. "The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol." Wellcome Open Research 6 (September 20, 2021): 240. http://dx.doi.org/10.12688/wellcomeopenres.17172.1.

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Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation. For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi. This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with S. pneumoniae serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population. Trial Registration: Pan African Clinical Trial Registry (REF: PACTR202008503507113)
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30

Lynch, Joyce M., David E. Briles, and Dennis W. Metzger. "Increased Protection against Pneumococcal Disease by Mucosal Administration of Conjugate Vaccine plus Interleukin-12." Infection and Immunity 71, no. 8 (2003): 4780–88. http://dx.doi.org/10.1128/iai.71.8.4780-4788.2003.

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ABSTRACT Streptococcus pneumoniae is a common cause of respiratory tract infections, its main entry route being the nasal mucosa. The recent development of pneumococcal polysaccharide conjugate vaccines has led to a dramatic improvement in protection against invasive disease in infants and children, but these vaccines have been found to be only 50 to 60% protective against bacterial carriage. In this study, we investigated the efficacy of intranasal (i.n.) conjugate vaccine delivery using interleukin-12 (IL-12) as a mucosal adjuvant. Immunized mice treated with IL-12 demonstrated increased expression of lung and splenic gamma interferon and IL-10 mRNAs; high levels of antibody, particularly serum immunoglobulin G2a (IgG2a) and respiratory IgA; and significantly increased opsonic activity. After intraperitoneal challenge with type 3 pneumococci, there was 75% survival of i.n. vaccinated mice compared to 0% survival of unvaccinated mice. In addition, after i.n. challenge with type 14 pneumococci, vaccinated mice possessed fewer bacterial colonies in the upper respiratory tract than unvaccinated mice. However, no significant difference in type 14 carriage was observed between vaccinated and unvaccinated groups following intramuscular vaccination, the typical route of vaccination in humans. Using mice with a genetic disruption in IgA expression, it was found that pneumococcus-specific IgA played a significant role in the clearance of bacteria from the upper respiratory tract. We conclude that i.n vaccination in the presence of IL-12 is able to enhance systemic and mucosal immune responses to pneumococci and efficiently protect against both invasive infection and bacterial carriage.
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31

STEENS, A., D. F. VESTRHEIM, I. S. AABERGE, et al. "A review of the evidence to inform pneumococcal vaccine recommendations for risk groups aged 2 years and older." Epidemiology and Infection 142, no. 12 (2014): 2471–82. http://dx.doi.org/10.1017/s0950268814001514.

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SUMMARYFor decades, vaccination with the 23-valent polysaccharide pneumococcal vaccine (PPV23) has been available for risk groups aged ⩾2 years to prevent invasive pneumococcal disease (IPD). Recently, a 13-valent pneumococcal conjugated vaccine (PCV13) has been licensed for use in all age groups. PCV13 may induce better protection than PPV23 because of different immunogenic properties. This called for a revision of vaccine recommendations for risk groups. We therefore reviewed literature on risk groups for IPD, and effectiveness and safety of pneumococcal vaccines and supplemented that with information from public health institutes, expert consultations and data on IPD epidemiology. We included 187 articles. We discuss the implications of the heterogenic vulnerability for IPD within and between risk groups, large indirect effects of childhood immunization, and limited knowledge on additional clinical benefits of PCV13 in combination with PPV23 for the Norwegian recommendations. These are now step-wise and consider the need for vaccination, choice of pneumococcal vaccines, and re-vaccination interval by risk group.
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Lebon, Ankie, Nelianne J. Verkaik, Joost A. M. Labout, et al. "Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study." Infection and Immunity 79, no. 4 (2011): 1680–87. http://dx.doi.org/10.1128/iai.01379-10.

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ABSTRACTThe currently available pneumococcal vaccines do not protect against all serotypes ofStreptococcus pneumoniae. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (n= 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.
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33

Walekhwa, Michael, Fiona Maiyo, Teresa Kerubo, and Fred Kipsang. "In Vitro Evaluation of Effect of Storage Time on Immunogenicity of the 10-Valent Pneumococcal Conjugate Vaccine Using Baby Rabbit Complement & HL-60 Cells." Kabarak Journal of Research & Innovation 14, no. 01 (2024): 16–25. http://dx.doi.org/10.58216/kjri.v14i01.280.

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Background: The efficacy and effectiveness of a vaccine is influenced by several factors including storage duration. Additionally, vaccines may be sufficiently administered but functionality of antibody generated may be hampered with by other factors such as nutritional status of the patient. As such, one of the ways of assessing vaccine efficacy is assessing the functionality of the antibodies generated. The 10v-PCV is a highly effective vaccine used to prevent invasive pneumococcal diseases in children. However, here in Kenya, cases of pneumococcal diseases are high and challenging to treat. This study thus aimed to evaluate the effect of storage of PCV-10 storage time on the functionality of Abs generated. Methodology; An in vitro experimental research design was employed for this study. opsonophagocytic activity assay using HL-60 Cells & Baby rabbit complement was used to assess whether or not the Pneumococci Serotype IgG antibodies elicited following administration with 10v-PCV vaccine are functional. Only 10v-PCV vaccine with same production date were procured. Twenty experimental rabbits of same gender were procured and used injected intraperitoneally with 3 doses of 100µl (0.34g) of 10v-PCV vaccine after every four weeks. Antibody functionality was then assessed using the opsonophagocytic activity assay method. Results: An average of 28.9% of pneumococcus exposed to the vaccine-induced secreted antibodies were killed by the pneumococcal IgG antibody. The highest percentage of number of bacteria killed was achieved after the 3rd dose of vaccination. There was no significant influence of storage duration on opsonophagocytic activity of generated antibodies. Conclusion: Storing of 10v-PCV vaccine up to 12 weeks does not significantly affect the opsonophagocytic activity of pneumococcal IgG antibodies.
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34

Salt, Penny, Carly Banner, Sarah Oh, et al. "Social Mixing with Other Children during Infancy Enhances Antibody Response to a Pneumococcal Conjugate Vaccine in Early Childhood." Clinical and Vaccine Immunology 14, no. 5 (2007): 593–99. http://dx.doi.org/10.1128/cvi.00344-06.

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ABSTRACT Children who have siblings and/or who attend day care have higher rates of nasopharyngeal colonization with pneumococci than lone children do. Pneumococcal colonization is usually asymptomatic but is a prerequisite for invasive disease. We studied the effect of social mixing with other children on immunity to a pneumococcal vaccine. One hundred sixty children aged 1 year were immunized with a 7-valent conjugate pneumococcal vaccine. A blood sample was obtained before and 9 to 11 days after the vaccine. The concentration and avidity of antibody against vaccine pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) were studied in relation to pneumococcal carriage rate and measures of social mixing. Children with increased social mixing had higher antibody concentrations against serotypes 4, 9V, 14, and 23F than lone children did. The least-carried serotype, serotype 4, was the one of the most immunogenic. This contrasts with serotype 6B, the most common nasopharyngeal isolate but the least immunogenic. Social mixing in infancy enhances the immune response to a Streptococcus pneumoniae polysaccharide-protein conjugate vaccine at 1 year of age. Exposure to pneumococci in the first year of life may induce immunological priming. An alternative explanation is that differences in immunological experience, such as increased exposure to respiratory viral infections in early childhood, alters the response to vaccines perhaps by affecting the balance between Th1 and Th2 cytokines. The low immunogenicity of serotype 6B polysaccharide might make conditions more favorable for carriage of the 6B organism and explain why 6B pneumococci were more frequently isolated than other serotypes.
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Camargos, Paulo, Eliane Drumond, and Cristiana M. Nascimento-Carvalho. "Effect of pneumococcal conjugate vaccines on invasive pneumococcal disease." Lancet Infectious Diseases 21, no. 4 (2021): 453. http://dx.doi.org/10.1016/s1473-3099(21)00051-7.

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36

Croney, Christina M., Mamie T. Coats, Moon H. Nahm, David E. Briles, and Marilyn J. Crain. "PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine." Clinical and Vaccine Immunology 19, no. 6 (2012): 891–96. http://dx.doi.org/10.1128/cvi.05671-11.

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ABSTRACTPneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.
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Clarke, Stuart C. "Control of pneumococcal disease in the United Kingdom – the start of a new era." Journal of Medical Microbiology 55, no. 8 (2006): 975–80. http://dx.doi.org/10.1099/jmm.0.46579-0.

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In 2000, a multi-valent pneumococcal conjugate vaccine, known as Prevnar, was licensed for use in infants and young children in the USA. The subsequent introduction of the vaccine into the childhood immunization schedule in that country led to a significant decrease in pneumococcal disease. The vaccine is effective against invasive and non-invasive pneumococcal infection, can be used in young children as well as adults and, like all conjugate vaccines, provides long-lasting immunity. Moreover, it reduces the incidence of antibiotic resistance because a number of resistant serotypes are targeted by the vaccine. Prevnar, also known as Prevenar, has since been licensed in numerous countries, including the UK. On 8 February 2006, the Departments of Health in England, Scotland and Wales announced the inclusion of Prevenar in the childhood immunization schedule. This announcement has important implications for pneumococcal infection, disease surveillance and immunization policy in the UK.
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SMITH, M. D., J. STUART, N. J. ANDREWS, W. A. TELFER BRUNTON, and K. A. V. CARTWRIGHT. "Invasive pneumococcal infection in South and West England." Epidemiology and Infection 120, no. 2 (1998): 117–23. http://dx.doi.org/10.1017/s0950268897008522.

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Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5·2 and 20·4 per 100000 catchment population (P<0·001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P=0·019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines.
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Alvarez, Carlos A., Ronald G. Hall, Suzy Lin, Aaron R. Perkins, and Eric M. Mortensen. "Impact of PCV13 and PPSV23 Vaccination on Invasive Pneumococcal Disease in Adults with Treated Rheumatoid Arthritis: A Population-Based Study." Microorganisms 12, no. 10 (2024): 2073. http://dx.doi.org/10.3390/microorganisms12102073.

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On-time receipt of pneumococcal vaccines is essential in patients with rheumatoid arthritis (RA) as immunosuppressive medications increase their risk of invasive pneumococcal disease (IPD). However, data regarding the impact of timely administration of these vaccines on the risk of developing IPD are lacking for RA patients. We conducted a retrospective cohort study to assess the impact of on-time vaccination for pneumococcal conjugate vaccine (PCV) 13 and pneumococcal polysaccharide vaccine (PPSV) 23 in patients treated for RA on the development of IPD using national Veterans Affairs data from 2010 to 2018. Patients > 18 years of age, diagnosed with RA, and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. A total of 33,545 patients were included in the cohort. Non-compliance with PCV recommendations was associated with an increased risk of IPD in a multivariable logistic regression model. This finding was consistent whether IPD status was ascertained by International Classification of Diseases coding (OR 2.42, 95%CI 2.14–2.73) or microbiologic data (OR 1.64, 95%CI 1.26–2.14). Providers should actively seek opportunities to provide pneumococcal vaccinations to patients with RA, as their on-time administration is associated with a decreased risk of IPD.
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Farrar, Jennifer Loo, Miwako Kobayashi, Lana Childs, and Tamara Pilishvili. "21. Systematic Review and Meta-Analysis of Pneumococcal Vaccine Effectiveness against Invasive Pneumococcal Disease among Adults." Open Forum Infectious Diseases 8, Supplement_1 (2021): S134—S135. http://dx.doi.org/10.1093/ofid/ofab466.223.

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Abstract Background Two new pneumococcal conjugate vaccines (PCVs), PCV15 and PCV20, are anticipated to be licensed for use in U.S. adults in 2021. To help inform the U.S. Advisory Committee on Immunization Practices’ discussions on pneumococcal vaccine use among adults, we conducted a systematic review and meta-analysis. We specifically looked at efficacy or effectiveness of PCV13 and pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) in adults. Methods We conducted a search of English literature published from 1998 – February 2021 on PCV13 and PPSV23 efficacy or effectiveness studies using eight major databases. Studies targeting adults with immunocompromising conditions were excluded. Title and abstract screening of identified studies and data abstraction were performed by two reviewers. Results were stratified by vaccine product, outcome evaluated (vaccine type (VT) or all IPD), study design, and effect measure. Random effects models were used to pool estimates by stratum. Results Of 3,422 citations reviewed, we identified 26 IPD studies; 4 on PCV13, 22 on PPSV23, 18 with all IPD, and 17 with VT-IPD (Table) as an outcome. Only one randomized-controlled trial (RCT) was identified for PCV13 with an efficacy of 52% (95% CI: 22%, 77%) against all IPD and 75% (95% CI: 41%, 91%) against VT-IPD. A pooled vaccine effectiveness (VE) estimate from three observational studies evaluating PCV13 was 56% (95% CI: 32%, 71%; I2 =12.8) against VT-IPD. Two RCTs evaluating PPSV23 reported efficacies against all IPD ranging between 79-86%; an additional RCT reported no IPD cases during RCT. Vaccine effectiveness estimates from 14 observational studies evaluating PPSV23 ranged between 29-76% against all IPD. Pooled VE estimates from 12 observational studies showed PPSV23 effectiveness against VT-IPD was 38% (95% CI: 28% to 46%; I2 =40.8). Table. Efficacy and effectiveness studies against vaccine-type invasive pneumococcal disease Conclusion Evidence suggests both pneumococcal vaccines are effective against VT-IPD in adults. Given that PCV15 and PCV20 are expected to be licensed based on immunogenicity data and no clinical efficacy data are available for these new vaccines, the findings from this review will help inform policy discussions on use of the new PCVs among adults. Disclosures All Authors: No reported disclosures
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41

Oliveira, Giuliana S., Maria Leonor S. Oliveira, Eliane N. Miyaji, and Tasson C. Rodrigues. "Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies." Vaccines 9, no. 11 (2021): 1338. http://dx.doi.org/10.3390/vaccines9111338.

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The importance of Streptococcus pneumoniae has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect. However, serotype replacement is a well-known phenomenon that has occurred after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been reported for other PCVs. Therefore, it is possible that serotype replacement will continue to occur even with higher valence formulations, but the development of serotype-independent vaccines might overcome this problem. Alternative vaccines are under development in order to improve cost effectiveness, either using proteins or the pneumococcal whole cell. These approaches can be used as a stand-alone strategy or together with polysaccharide vaccines. Looking ahead, the next generation of pneumococcal vaccines can be impacted by the new technologies recently approved for human use, such as mRNA vaccines and viral vectors. In this paper, we will review the advantages and disadvantages of the addition of new polysaccharides in the current PCVs, mainly for low- and middle-income countries, and we will also address future perspectives.
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42

García, Ernesto. "Structure, Function, and Regulation of LytA: The N-Acetylmuramoyl-l-alanine Amidase Driving the “Suicidal Tendencies” of Streptococcus pneumoniae—A Review." Microorganisms 13, no. 4 (2025): 827. https://doi.org/10.3390/microorganisms13040827.

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Streptococcus pneumoniae (pneumococcus) is a significant human pathogen responsible for a range of diseases from mild infections to invasive pneumococcal diseases, particularly affecting children, the elderly, and immunocompromised individuals. Despite pneumococcal conjugate vaccines having reduced disease incidence, challenges persist due to serotype diversity, vaccine coverage gaps, and antibiotic resistance. This review highlights the role of LytA, a key autolysin (N-acetylmuramoyl-l-alanine amidase), in pneumococcal biology. LytA regulates autolysis, contributes to inflammation, and biofilm formation, and impairs bacterial clearance. It also modulates complement activation, aiding immune evasion. LytA expression is influenced by environmental signals and genetic regulation and is tied to competence for genetic transformation, which is an important virulence trait, particularly in meningitis. With the increase in antibiotic resistance, LytA has emerged as a potential therapeutic target. Current research explores its use in bacteriolytic therapies, vaccine development, and synergistic antibiotic strategies. Various compounds, including synthetic peptides, plant extracts, and small molecules, have been investigated for their ability to trigger LytA-mediated bacterial lysis. Future directions include the development of novel anti-pneumococcal interventions leveraging LytA’s properties while overcoming vaccine efficacy and resistance-related challenges. Human challenge models and animal studies continue to deepen our understanding of pneumococcal pathogenesis and potential treatment strategies.
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43

Bahy, Rehab H., Hayam M. Hamouda, Amal S. Shahat, Aymen S. Yassin, and Magdy A. Amin. "Development and evaluation of a novel vaccine against prevalent invasive multi-drug resistant strains ofStreptococcus pneumoniae." PeerJ 4 (November 30, 2016): e2737. http://dx.doi.org/10.7717/peerj.2737.

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Streptococcus pneumoniaeis a pathogen that causes serious invasive infections, such as septicemia, meningitis and pneumonia in addition to mild upper respiratory tract infections. Protection from pneumococcal diseases is thought to be mediated mainly by serotype-specific antibodies to capsular antigens. Pneumococcal conjugate vaccine consists of sugars (polysaccharides) from the capsule of the bacteriumS. pneumoniaethat are conjugated to a carrier protein. Three pneumococcal conjugated vaccines, each directed against a group of serotypes, are registered in Egypt; however, local vaccine production is required to cover the most prevalent serotypes. In this work, capsular polysaccharide from the most current and prevalent serotypes in Egypt were extracted, purified and conjugated to bovine serum albumin (BSA). The polysaccharide protein conjugate was purified through ultrafiltration technique and molecular size distribution was compared to an available vaccine. The immunogenicity of the prepared vaccine was examined via two methods: First, by measuring the levels of the elicited antibodies in the sera of the vaccinated mice; Second, by challenging the vaccinated groups of mice with approximately 107CFU of each specific serotype and determining the degree of protection the developled vaccine offers. Our results show that the developed conjugated capsular polysaccharide vaccine is highly immunogenic and protective in mice. This finding illustrates the importance of tracking the most recent and predominant peneumococcal serotypes to generate effective vaccines, instead of using expensive imported vaccines with large number of serotypes which might not be even present in the community.
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44

KYAW, M. H., S. CLARKE, I. G. JONES, and H. CAMPBELL. "Non-invasive pneumococcal disease and antimicrobial resistance: vaccine implications." Epidemiology and Infection 128, no. 1 (2002): 21–27. http://dx.doi.org/10.1017/s0950268801006331.

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We reviewed laboratory data on non-invasive pneumococcal isolates reported from all diagnostic laboratories in Scotland during the period 1988–99. Of 4491 isolates from hospitalized patients, 654 (64·7%) were from sputum, 79 (7·8%) from the nasopharynx and 278 (27·5%) from other superficial sites. The serogroups included in the 23-valent polysaccharide vaccine caused 96–9% of all non-invasive disease in all age groups. The 7-, 9-, and 11-valent conjugated vaccine serogroups were responsible for 87–94%, 85–93%, 74–81% and 75–84% of non-invasive disease respectively in age groups <2 years, [les ]5 years, [ges ]65 years and all ages. The coverage of non-susceptible penicillin and erythromycin non-invasive isolates was >99% and >95% with the 23-valent polysaccharide and 7–11-valent conjugate vaccines respectively. The eight most common serogroups were 23, 9, 6, 19, 14, 3, 15 and 11 (in descending order). The serogroups associated with antimicrobial resistance in non-invasive disease were similar to those found in invasive disease. The finding of a similar serogroup distribution in both invasive and non-invasive disease (regardless of the site of clinical isolate), is consistent with serogroups colonizing non-sterile sites and having the potential to invade. The availability of conjugated vaccines reinforces the importance of systematic surveillance to determine accurately and regularly the coverage of pneumococcal serogroups and types causing both invasive and non-invasive disease.
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45

Koroleva, I. S., G. V. Beloshitsky, M. A. Koroleva, and A. A. Mel’Nikova. "Epidemiological Aspects of Pneumococcal Meningitis in the Russian Federation." Epidemiology and Vaccine Prevention 15, no. 5 (2016): 6–13. http://dx.doi.org/10.31631/2073-3046-2016-15-5-6-13.

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Introduction. Pneumococcal meningitis (PM) refers to severe manifestations of pneumococcal disease with high mortality and frequent post-infectious complications. In the context of the introduction of vaccination against pneumococcal infections in the Russian Federation healthcare practice increases the importance of close monitoring of the spread of the PM in the country, identifying areas of concern, the definition of risk and serotype structure of pneumococcus, which is an essential component of the assessment of the effectiveness of vaccination. Materials and methods. We collected 1380 cases identified by the PM on the territory of the Russian Federation in 2010 - 2014. We analyzed the incidence, mortality, mortality, age distribution, social belonging PM patients in the whole country, and in the federal districts. Determined serotype affiliation 35 pneumococcal strains isolated from patients with PM in Russia in 2015. Results. The proportion of pneumococci in the etiological structure of bacterial meningitis during the 2010 - 2014 fluctuated in the range of 18.4 - 24.8% and averaged 22.1%. The incidence of the PM in the Russian Federation in 2010 - 2014 determined at the level of 0.19, the death rate - 0.03. The level of mortality in pneumococcal meningitis in the Russian Federation in 2010 - 2014 increased from 13 (2010) to 21.1% (2014), the average was 17.1%. The most vulnerable age groups were adults over 25 years old and children up to 6 years. Among children under the age of 6 years mortality was 10.7%. The study of serotypes of 35 pneumococcal strains showed that in 2015 serotype structure of invasive pneumococcal vaccine serotypes maintained dominance, the proportion reached 75% for PCV13 and 54% for PCV10. Conclusion. The problem of pneumococcal meningitis remains valid in the Russian Federation. Active use of vaccines, especially in children, will reduce the incidence of this infection and the severity of its consequences.
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46

Deng, James Z., Jason Lin, Michelle Chen, Catherine Lancaster, and Ping Zhuang. "Characterization of High Molecular Weight Pneumococcal Conjugate by SEC-MALS and AF4-MALS." Polymers 14, no. 18 (2022): 3769. http://dx.doi.org/10.3390/polym14183769.

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Infections by Streptococcus pneumoniae can cause serious pneumococcal diseases and other medical complications among patients. Polysaccharide-based vaccines have been successfully developed as prophylactic agents against such deadly bacterial infections. In the 1980s, PNEUMOVAX® 23 were introduced as the first pneumococcal polysaccharide vaccines (PPSV). Later, pneumococcal polysaccharides were conjugated to a carrier protein to improve immune responses. Pneumococcal conjugate vaccines (PCV) such as PREVNAR® and VAXNEUVANCE™ have been developed. Of the more than 90 pneumococcal bacteria serotypes, serotype 1 (ST-1) and serotype 4 (ST-4) are the two main types that cause invasive pneumococcal diseases (IPD) that could lead to morbidity and mortality. Development of a novel multi-valent PCV against these serotypes requires extensive biophysical and biochemical characterizations of each monovalent conjugate (MVC) in the vaccine. To understand and characterize these high molecular weight (Mw) polysaccharide protein conjugates, we employed the multi-angle light scattering (MALS) technique coupled with size-exclusion chromatography (SEC) separation and asymmetrical flow field flow fractionation (AF4). MALS analysis of MVCs from the two orthogonal separation mechanisms helps shed light on the heterogeneity in conformation and aggregation states of each conjugate.
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47

Dullius, Cynthia Rocha, Luciana Zani, and José Miguel Chatkin. "Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital." Jornal Brasileiro de Pneumologia 44, no. 5 (2018): 361–66. http://dx.doi.org/10.1590/s1806-37562017000000056.

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ABSTRACT Objective: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). Methods: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. Results: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. Conclusions: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.
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48

Konradsen, Helle Bossen, and Margit Staum Kaltoft. "Invasive Pneumococcal Infections in Denmark from 1995 to 1999: Epidemiology, Serotypes, and Resistance." Clinical and Vaccine Immunology 9, no. 2 (2002): 358–65. http://dx.doi.org/10.1128/cdli.9.2.358-365.2002.

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ABSTRACT Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.
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49

Malcheva, Mariya. "STREPTOCOCCUS PNEUMONIAE SEROTYPE DISTRIBUTION AFTER THE INTRODUCTION OF PNEUMOCOCCAL CONJUGATE VACCINES." PROBLEMS of Infectious and Parasitic Diseases 47, no. 1 (2019): 5–8. http://dx.doi.org/10.58395/pipd.v47i1.10.

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Streptococcus pneumoniae serotypes are changing due to the widely introduced pneumococcal conjugate vaccines. Surveillance studies have proven valuable in monitoring these vaccine effects. S. pneumoniae is highly adaptable to its human reservoir and colonises mucosal surfaces of upper airways mainly in children. Carriage decreases during the first 2 years of life because of the development of naturally acquired adaptive immune memory. Most of the serotypes do not cause serious illnesses but few of them are responsible for severe pneumococcal infections. Ten of the most common serotypes are estimated to cause over 60% of invasive diseases worldwide. The virulence factor of S. pneumoniae is the polysaccharide capsule as non-encapsulated strains are absent among the strains causing invasive pneumococcal disease. Prevalence of serotypes differs depending on the age group and geographic area of patients. Differences in PCV implementation lead to changes in serotype distribution and to significant reduction of disease caused by vaccine types.
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50

Pai, Uday A., Srinivas G. Kasi, Nehal Patel, and Varsha Narayanan. "Pneumococcal Conjugate Vaccines in India: Reviewing Disease Burden, Serotypes, Vaccine Choice and Dosing Schedules." Asian Journal of Pediatric Research 15, no. 3 (2025): 52–65. https://doi.org/10.9734/ajpr/2025/v15i3433.

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India has almost a quarter of the global childhood pneumonia burden, with an estimated 8 million severe cases, more than 50% of whom need hospitalization or even intensive care, constituting a huge health burden. India sees at least 0.1 million deaths due to pneumococcal infections every year in children below 5 years of age. Fatality rates in pneumococcal infections are overall 6-7%, ranging from 11% in severe cases to 60% in hospitalized cases and invasive pneumococcal disease (IPD). Almost half of pneumococcal infections show resistance to antibiotics, and therefore prevention via vaccination is the best approach. The inclusion of pneumococcal vaccination in the Universal Immunization Programme (UIP) of India in 2017 has been a required and welcome move. The purpose of this article is to review the pneumonia burden, pneumococcal serotypes in India, and the various available pneumococcal conjugate vaccines (PCVs) with their features and coverage to understand clinical relevance and make informed decisions. Further areas of research include impact studies of PCV in India, as well as evolving serotype prevalence for developing future relevant vaccines.
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