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1
Sheibak, V. M., and M. V. Haretskaya. "DEVELOPMENT OF VACCINES FOR SARS-COV-2." Journal of the Grodno State Medical University 20, no. 1 (2022): 5–12. http://dx.doi.org/10.25298/2221-8785-2022-20-1-5-12.
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Background. Currently, an active search for effective vaccines against the SARS-CoV-2 coronavirus continues. Purpose. To analyze the literature and assess the status of active vaccine development against SARS-CoV-2. Material and methods. We analyzed Russian and English language literature sources on the problem of finding an effective vaccine against SARS-CoV-2. Results. Structural proteins of the coronavirus have been analyzed as basic compounds for the development of vaccines. It was found that protein S is an ideal structure for creating vaccines that effectively induce the synthesis of neutralizing antibodies and provide the formation of immunity. Information about current trends in vaccine development has been obtained. Conclusions. The SARS-CoV-2 virus continues to mutate, which leads to the emergence of new highly contagious strains such as Delta, Omicron. In this regard, more research and clinical trials are needed to confirm the effectiveness of the current SARS-CoV-2 vaccines, or to continue developing the new ones.
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Bretón I, Andrea, and Alejandro Afani S. "Vacunas SARS-CoV-2." Revista Hospital Clínico Universidad de Chile 32, no. 2 (2021): 168–76. http://dx.doi.org/10.5354/2735-7996.2021.69660.
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Vaccines are biological products that stimulate the immune system to generate specific responses and immune memory. Faced with the magnitude of the problem caused by the Covid-19 pandemic, there is an urgent need to find an effective and safe preventive intervention. The race to find the ideal vaccine against this new coronavirus has required optimizing research times on this topic. Currently, more than 200 SARS-CoV-2 vaccine candidates are in development, 177 in preclinical evaluation, 63 in clinical evaluation and 16 of them in phase 3 of clinical trials. In our country, 3 SARS-CoV-2 vaccines are already authorized for administration, which have demonstrated safety and efficacy in clinical trials.
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Bellamkonda, Navya, Upendra Pradeep Lambe, Sonali Sawant, Shyam Sundar Nandi, Chiranjib Chakraborty, and Deepak Shukla. "Immune Response to SARS-CoV-2 Vaccines." Biomedicines 10, no. 7 (2022): 1464. http://dx.doi.org/10.3390/biomedicines10071464.
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COVID-19 vaccines have been developed to confer immunity against the SARS-CoV-2 infection. Prior to the pandemic of COVID-19 which started in March 2020, there was a well-established understanding about the structure and pathogenesis of previously known Coronaviruses from the SARS and MERS outbreaks. In addition to this, vaccines for various Coronaviruses were available for veterinary use. This knowledge supported the creation of various vaccine platforms for SARS-CoV-2. Before COVID-19 there are no reports of a vaccine being developed in under a year and no vaccine for preventing coronavirus infection in humans had ever been developed. Approximately nine different technologies are being researched and developed at various levels in order to design an effective COVID-19 vaccine. As the spike protein of SARS-CoV-2 is responsible for generating substantial adaptive immune response, mostly all the vaccine candidates have been targeting the whole spike protein or epitopes of spike protein as a vaccine candidate. In this review, we have compiled the immune response to SARS-CoV-2 infection and followed by the mechanism of action of various vaccine platforms such as mRNA vaccines, Adenoviral vectored vaccine, inactivated virus vaccines and subunit vaccines in the market. In the end we have also summarized the various adjuvants used in the COVID-19 vaccine formulation.
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Ebrahim, Fawzi, Salah Tabal, Yosra Lamami, et al. "Anti-SARS-CoV-2 IgG Antibodies Post-COVID-19 or Post-Vaccination in Libyan Population: Comparison of Four Vaccines." Vaccines 10, no. 12 (2022): 2002. http://dx.doi.org/10.3390/vaccines10122002.
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Measurement of strength and durability of SARS-COV-2 antibody response is important to understand the waning dynamics of immune response to both vaccines and infection. The study aimed to evaluate the level of IgG antibodies against SARS-CoV-2 and their persistence in recovered, naïve, and vaccinated individuals. We investigated anti-spike RBD IgG antibody responses in 10,000 individuals, both following infection with SARS-CoV-2 and immunization with SARS-COV-2 AstraZeneca, Sputnik V, Sinopharm, and Sinovac. The mean levels of anti-spike IgG antibodies were higher in vaccinated participants with prior COVID-19 than in individuals without prior COVID-19. Overall, antibody titers in recovered vaccinee and naïve vaccinee persisted beyond 20 weeks. Vaccination with adenoviral–vector vaccines (AstraZeneca and Sputnik V) generates higher antibody titers than with killed virus vaccine (Sinopharm and Sinovac). Approximately two-thirds of asymptomatic unvaccinated individuals had developed virus-specific antibodies. A single dose of vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with apparent prior SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals. In addition, the high number of seropositivity among asymptomatic unvaccinated individuals showed that the number of infections are probably highly underestimated. Those vaccinated with inactivated vaccine may require more frequent boosters than those vaccinated with adenoviral vaccine. These findings are important for formulating public health vaccination strategies during COVID-19 pandemic.
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ISI-SENAI-CIMATEC Group and Development and Innovation Laboratory of Butantan Institute. "Vaccines’ Candidates Against SARS-CoV-2." JOURNAL OF BIOENGINEERING AND TECHNOLOGY APPLIED TO HEALTH 3, no. 2 (2020): 249–66. http://dx.doi.org/10.34178/jbth.v3i2.126.
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Scientists, health organizations, and pharmaceutical companies are making a large global effort to develop vaccines against SARS-CoV-2, the virus of COVID-19 since the outbreak began. Until now, we have more than 150 candidates. However, 19 vaccine candidates have entered clinical trials in phase 2 and 3 trials (31 July 2020). In this article we aimed to present the platforms for COVID-19 vaccine, the types of vaccines (live, attenuated, inactivated, DNA/RNA, proteins subunits, viral vector), the antigen selection, adjuvants, and we focused on the phase 2/3 trial vaccines at this point (Sinopharm, Coronavac, Moderna, Oxford, Biontech). We searched the data in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Excerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews, and original articles in this order. We reviewed 216 articles and used 106 from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-SARS-2, COVID-19, corona virus, coronaviruses, vaccine, platform, antigen, subunit, live and attenuated vaccine, RNA vaccine, live vaccine, inactivated vaccine, types of vaccines, adjuvants, replication, viral vector, phase 1-3, trial, with the tools MeSH (Medical Subject Headings), AND, OR, and the characters [,“,; /., to ensure the best review topics. We concluded that although vaccines have shown safety in phase 1 and efficacy in phase 2 and the beginning of phase 3 is starting, the most renowned scientists believe that a vaccine will be available only in the middle of next year.
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Geng, Qibin, Wanbo Tai, Victoria K. Baxter, et al. "Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection." PLOS Pathogens 17, no. 9 (2021): e1009897. http://dx.doi.org/10.1371/journal.ppat.1009897.
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The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.
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Walker, Karrie. "SARS-CoV-2 Vaccine." Global Reproductive Health 5, no. 3 (2020): e42-e42. http://dx.doi.org/10.1097/grh.0000000000000042.
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Zhang, Qiong, Shashi Tiwari, Jing Wen, et al. "Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains in mice." PLOS ONE 19, no. 4 (2024): e0300524. http://dx.doi.org/10.1371/journal.pone.0300524.
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To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.
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Hou, Xu-Chen, Hui-Fang Xu, Yang Liu, et al. "A Vaccine with Multiple Receptor-Binding Domain Subunit Mutations Induces Broad-Spectrum Immune Response against SARS-CoV-2 Variants of Concern." Vaccines 10, no. 10 (2022): 1653. http://dx.doi.org/10.3390/vaccines10101653.
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With the emergence of more variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune evasion of these variants from existing vaccines, the development of broad-spectrum vaccines is urgently needed. In this study, we designed a novel SARS-CoV-2 receptor-binding domain (RBD) subunit (RBD5m) by integrating five important mutations from SARS-CoV-2 variants of concern (VOCs). The neutralization activities of antibodies induced by the RBD5m candidate vaccine are more balanced and effective for neutralizing different SARS-CoV-2 VOCs in comparison with those induced by the SARS-CoV-2 prototype strain RBD. Our results suggest that the RBD5m vaccine is a good broad-spectrum vaccine candidate able to prevent disease from several different SARS-CoV-2 VOCs.
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Thomas, Whitney, Adam Albano, Dean Kirkel, Nason Rouhizad, and Folasade Arinze. "Immune Thrombocytopenic Purpura following Administration of mRNA-Based SARS-CoV-2 and MMR Vaccinations: A Cautionary Tale." Case Reports in Infectious Diseases 2021 (October 9, 2021): 1–4. http://dx.doi.org/10.1155/2021/2704249.
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We report a case of immune thrombocytopenic purpura (ITP) in an otherwise healthy 31-year-old man following coadministration of the live measles, mumps, and rubella (MMR) vaccine with the Pfizer-BioNTech mRNA SARS-CoV-2 vaccine. The patient was hospitalized briefly and treated for ITP with glucocorticoids, IVIG, and platelet transfusion. Although our patient’s clinical presentation and subsequent course are similar to those of other cases of ITP in association with SARS-CoV-2 vaccination, to our knowledge, this is the first reported case of ITP following MMR and mRNA SARS-CoV-2 vaccine coadministration. It would be impossible to conclusively prove that the patient’s thrombocytopenia was secondary to the SARS-CoV-2 vaccine alone, the MMR vaccine, or an additive effect of both vaccines. However, with the CDC guidelines recommending the coadministration of the mRNA SARS-CoV-2 vaccine without regards to timing with other vaccines, we urge further caution as there is limited evidence to inform practice. This case highlights the need for further safety data regarding the coadministration and timing of the mRNA SARS-CoV-2 vaccine with other vaccines.
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Evans, John P., and Shan-Lu Liu. "Challenges and Prospects in Developing Future SARS-CoV-2 Vaccines: Overcoming Original Antigenic Sin and Inducing Broadly Neutralizing Antibodies." Journal of Immunology 211, no. 10 (2023): 1459–67. http://dx.doi.org/10.4049/jimmunol.2300315.
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Abstract The impacts of the COVID-19 pandemic led to the development of several effective SARS-CoV-2 vaccines. However, waning vaccine efficacy as well as the antigenic drift of SARS-CoV-2 variants has diminished vaccine efficacy against SARS-CoV-2 infection and may threaten public health. Increasing interest has been given to the development of a next generation of SARS-CoV-2 vaccines with increased breadth and effectiveness against SARS-CoV-2 infection. In this Brief Review, we discuss recent work on the development of these next-generation vaccines and on the nature of the immune response to SARS-CoV-2. We examine recent work to develop pan-coronavirus vaccines as well as to develop mucosal vaccines. We further discuss challenges associated with the development of novel vaccines including the need to overcome “original antigenic sin” and highlight areas requiring further investigation. We place this work in the context of SARS-CoV-2 evolution to inform how the implementation of future vaccine platforms may impact human health.
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Zeedan, Gamil S. G., Abeer M. Abdalhamed, Amel M. Naguib, Said I. A. Shalaby, Mona A. M. Awad, and Mervat I. Abd El Moniem. "An Overview of Adenovirus Vector-based Vaccines against SARS-CoV-2." World's Veterinary Journal 13 (March 25, 2023): 12–25. http://dx.doi.org/10.54203/scil.2023.wvj2.
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Adenovirus vectors have been employed to develop a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for curtailing the Covid-19 pandemic spreading. Many different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as an antigen. Spike (S) protein is comprised of S1 and S2 subunits, in which the receptor-binding domain (RBD) of S1 is responsible for recognizing and engaging with its host cellular receptor protein angiotensin-converting enzyme 2 (ACE2), S2 accounts for membrane fusion of virus and host cell. Chimpanzee adenovirus was also used as a vector vaccine for SARS-CoV-2 (ChAdSARS-CoV-2-S) by intramuscular injection, and intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced, with several vaccines receiving Emergency Use Authorization (EUA). It was shown that rhesus macaques were protected from SARS-CoV-2 challenge after a month of being vaccinated with ChAd-SARS-CoV-2-S. A single intranasal or two intramuscular ChAd-SARSCoV-2-S vaccines could induce humoral antibodies and T cell responses to protect the upper and lower respiratory tract against SARS-CoV-2. As the effectiveness was demonstrated in non-human primates, ChAd-SARS-CoV-2-Sa potential option for preventing SARS-CoV-2 infection in humans. However, detecting novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs monitoring. Moreover, the cause of recently documented rare cases of vaccine indicated immune thrombotic thrombocytopenia. This review article provided details for the adenovirus vector vaccine for SARS-CoV-2 in humans and tried to provide solutions to the adenovirus vector hemagglutinin issue.
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Sundaram, Appavu K., Daniel Ewing, Zhaodong Liang, et al. "Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice." Pathogens 10, no. 5 (2021): 626. http://dx.doi.org/10.3390/pathogens10050626.
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The development of a safe and effective vaccine to protect against COVID-19 is a global priority due to the current high SARS-CoV-2 infection rate. Currently, there are over 160 SARS-CoV-2 vaccine candidates at the clinical or pre-clinical stages of development. Of these, there are only three whole-virus vaccine candidates produced using β-propiolactone or formalin inactivation. Here, we prepared a whole-virus SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) using a novel psoralen inactivation method and evaluated its immunogenicity in mice using two different adjuvants, alum and Advax-2. We compared the immunogenicity of SARS-CoV-2 PsIV against SARS-CoV-2 DNA vaccines expressing either full-length or truncated spike proteins. We also compared the psoralen-inactivated vaccine against a DNA prime, psoralen-inactivated vaccine boost regimen. After two doses, the psoralen-inactivated vaccine, when administered with alum or Advax-2 adjuvants, generated a dose-dependent neutralizing antibody responses in mice. Overall, the pattern of cytokine ELISPOT responses to antigen-stimulation observed in this study indicates that SARS-CoV-2 PsIV with the alum adjuvant promotes a Th2-type response, while SARS-CoV-2 PsIV with the Advax-2 adjuvant promotes a Th1-type response.
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Julia, San Miguel Rodríguez, Rodríguez Barbero Julita, San Miguel Hernández Angel, San Miguel Rodríguez Angel, and San Miguel Rodríguez María. "Vaccines against SARS-COV-2." GSC Advanced Research and Reviews 8, no. 2 (2021): 045–57. https://doi.org/10.5281/zenodo.5195600.
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Vaccines against Covid-19 were developed on the basis of protein S, before it had the mutations identified in these variants. Although research conducted so far is less effective against variants and continues to offer protection against severe forms of Covid-19, further research is ongoing. WHO is working with every country in the world to help coordinate the key stages of this vaccine manufacturing and development process. In particular, to facilitate equitable access for all countries to vaccines against Covid-19 and that they are safe and effective for the billions of people who need them.
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Sanders, John W., Daniel Ewing, Appavu K. Sundaram, et al. "Immunogenicity and Protective Efficacy of Psoralen-Inactivated SARS-CoV-2 Vaccine in Nonhuman Primates." Vaccines 12, no. 5 (2024): 451. http://dx.doi.org/10.3390/vaccines12050451.
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COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted public health and the economy worldwide. Most of the currently licensed COVID-19 vaccines act by inhibiting the receptor-binding function of the SARS-CoV-2 spike protein. The constant emergence of SARS-CoV-2 variants resulting from mutations in the receptor-binding domain (RBD) leads to vaccine immune evasion and underscores the importance of broadly acting COVID-19 vaccines. Inactivated whole virus vaccines can elicit broader immune responses to multiple epitopes of several antigens and help overcome such immune evasions. We prepared a psoralen-inactivated SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) and evaluated its immunogenicity and efficacy in nonhuman primates (NHPs) when administered with the Advax-CpG adjuvant. We also evaluated the SARS-CoV-2 PsIV as a booster shot in animals vaccinated with a DNA vaccine that can express the full-length spike protein. The Advax-CpG-adjuvanted SARS-CoV-2 PsIV elicited a dose-dependent neutralizing antibody response in the NHPs, as measured using a serum microneutralization assay against the SARS-CoV-2 Washington strain and the Delta variant. The animals vaccinated with the DNA vaccine followed by a boosting dose of the SARS-CoV-2 PsIV exhibited the highest neutralizing antibody responses and were able to quickly clear infection after an intranasal challenge with the SARS-CoV-2 Delta variant. Overall, the data show that the Advax-CpG-adjuvanted SARS-CoV-2 PsIV, either by itself or as a booster shot following nucleic acid (NA) vaccines, has the potential to protect against emerging variants.
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Dénes, Béla, Ryan N. Fuller, Wayne Kelin, et al. "A CTB-SARS-CoV-2-ACE-2 RBD Mucosal Vaccine Protects Against Coronavirus Infection." Vaccines 11, no. 12 (2023): 1865. http://dx.doi.org/10.3390/vaccines11121865.
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Mucosal vaccines protect against respiratory virus infection by stimulating the production of IgA antibodies that protect against virus invasion of the mucosal epithelium. In this study, a novel protein subunit mucosal vaccine was constructed for protection against infection by the beta coronavirus SARS-CoV-2. The vaccine was assembled by linking a gene encoding the SARS-CoV-2 virus S1 angiotensin converting enzyme receptor binding domain (ACE-2-RBD) downstream from a DNA fragment encoding the cholera toxin B subunit (CTB), a mucosal adjuvant known to stimulate vaccine immunogenicity. A 42 kDa vaccine fusion protein was identified in homogenates of transformed E. coli BL-21 cells by acrylamide gel electrophoresis and by immunoblotting against anti-CTB and anti-ACE-2-RBD primary antibodies. The chimeric CTB-SARS-CoV-2-ACE-2-RBD vaccine fusion protein was partially purified from clarified bacterial homogenates by nickel affinity column chromatography. Further vaccine purification was accomplished by polyacrylamide gel electrophoresis and electro-elution of the 42 kDa chimeric vaccine protein. Vaccine protection against SARS-CoV-2 infection was assessed by oral, nasal, and parenteral immunization of BALB/c mice with the CTB-SARS-CoV-2-ACE-2-RBD protein. Vaccine-induced SARS-CoV-2 specific antibodies were quantified in immunized mouse serum by ELISA analysis. Serum from immunized mice contained IgG and IgA antibodies that neutralized SARS-CoV-2 infection in Vero E6 cell cultures. In contrast to unimmunized mice, cytological examination of cell necrosis in lung tissues excised from immunized mice revealed no detectable cellular abnormalities. Mouse behavior following vaccine immunization remained normal throughout the duration of the experiments. Together, our data show that a CTB-adjuvant-stimulated CTB-SARS-CoV-2-ACE-2-RBD chimeric mucosal vaccine protein synthesized in bacteria can produce durable and persistent IgA antibodies in mice that neutralize the SARS-CoV-2 subvariant Omicron BA.1.1.
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Seo, Sang Heui, and Yunyueng Jang. "Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection." Vaccines 8, no. 4 (2020): 584. http://dx.doi.org/10.3390/vaccines8040584.
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A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe a cold-adapted live-attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22 °C/2020) developed by gradually adapting the growth of SARS-CoV-2 from 37 °C to 22 °C in Vero cells. This vaccine can be potentially administered to humans as a nasal spray. Its single dose strongly induced neutralising antibodies (titre > 640), cellular immunity, and mucosal IgA antibodies in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infections. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show body weight loss, death, or the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. These results demonstrate that the cold-adapted live attenuated SARS-CoV-2 vaccine we have developed may be a candidate SARS-CoV-2 vaccine for humans.
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Stafford, Lauren Stewart, Vivian Valcarce Luaces, Joseph Neu, et al. "Effect of SARS-CoV-2 vaccine on the breastmilk antibody response among lactating healthcare workers." Journal of Immunology 206, no. 1_Supplement (2021): 30.15. http://dx.doi.org/10.4049/jimmunol.206.supp.30.15.
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Abstract In 2019, a deadly virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19, emerged. Two mRNA-based COVID-19 vaccines were approved for use in December 2020 in the US and have begun providing immunity to those receiving the vaccination. Certain vaccines given to pregnant and lactating mothers provide immunity to infants through transmission across the placenta and umbilical cord (IgG) and breast milk (IgA). Breastmilk produced by mothers with a history of COVID-19 infection has found to be a source of anti-SARS-CoV-2 IgA and IgG. This study aimed to determine the presence of specific SARS-CoV-2 IgA in the breastmilk of lactating women after the COVID-19 vaccine administration. As such, lactating healthcare workers who received the SARS-CoV-2 mRNA vaccine (Pfizer-BioNtech or Moderna) made up a sample group. Plasma and breast milk were collected at three time points (pre-vaccination, 14–28 days post first dose of vaccine, and 7 days post second dose of vaccine). SARS-CoV-2 specific IgA (breastmilk) and IgG (plasma) concentration were then measured by ELISA. We found consistent secretion of SARS-CoV-2 specific IgA in breast milk after COVID-19 vaccination. The second dose of the SARS-CoV-2 vaccine was necessary to elicit IgA response in breastmilk detectable by ELISA. There is a correlation of the level of SARS-CoV-2 specific IgG in blood with SARS-CoV-2 specific IgA in breastmilk. Our results show that the mRNA-based COVID-19 vaccines from Pfizer-BioNTech and Moderna induce SARS-CoV-2 specific IgA secretion in breastmilk. Further studies are needed to determine the duration of this immune response and a possible passive immunity transfer of SARS-CoV-2 specific IgA to breastfeeding infants.
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Lu, Baojing, Ling Tao, Ting Wang, et al. "Humoral and Cellular Immune Responses Induced by 3a DNA Vaccines against Severe Acute Respiratory Syndrome (SARS) or SARS-Like Coronavirus in Mice." Clinical and Vaccine Immunology 16, no. 1 (2008): 73–77. http://dx.doi.org/10.1128/cvi.00261-08.
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ABSTRACT Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. Here, we studied the immunogenicity of human SARS-CoV 3a and bat SL-CoV 3a DNA vaccines in mice through electroporation immunization followed by enzyme-linked immunosorbent, enzyme-linked immunospot, and flow cytometry assays. Our results showed that high levels of specific humoral responses were induced by SARS-CoV 3a and SL-CoV 3a DNA vaccines. Furthermore, a strong Th1-based cellular immune response was stimulated by both DNA vaccines. The vaccines stimulated gamma interferon production mainly by CD8+ T cells and interleukin-2 (IL-2) mainly by CD4+ T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.
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Shen, Ching-Ju, Yen-Pin Lin, Shu-Yu Hu, et al. "Pilot Study for Immunogenicity of SARS-CoV-2 Vaccine with Seasonal Influenza and Pertussis Vaccines in Pregnant Women." Vaccines 11, no. 1 (2023): 119. http://dx.doi.org/10.3390/vaccines11010119.
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Background: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. Methods: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. Results: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. Conclusion: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions.
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Liu, Ying, and Qing Ye. "Nucleic Acid Vaccines against SARS-CoV-2." Vaccines 10, no. 11 (2022): 1849. http://dx.doi.org/10.3390/vaccines10111849.
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The coronavirus disease 2019 (COVID-19) has spread worldwide and imposed a substantial burden on human health, the environment, and socioeconomic development, which has also accelerated the process of nucleic acid vaccine development and licensure. Nucleic acid vaccines are viral genetic sequence-based vaccines and third-generation vaccines after whole virus vaccines and recombinant subunit vaccines, including DNA vaccines and RNA vaccines. They have many unique advantages, but there are many aspects that require optimization. Therefore, the purpose of this review is to discuss the research and development processes of nucleic acid vaccines, summarize the advantages and shortcomings, and propose further optimization strategies by taking COVID-19 vaccines as an example. Hopefully, this work can make a modest contribution in promoting the construction of emergency nucleic acid vaccine platforms and in avoiding the reemergence of similar public health emergencies.
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Floriam, Krammer, and Joabis Martins. "SARS-CoV-2 vaccines in development." SARS-CoV-2 vaccines in development 586, no. 516 (2020): 527. https://doi.org/10.5281/zenodo.10899652.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019(COVID-19) pandemic. To mitigate the effects of the virus on public health, theeconomy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years.
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Qiao, Rui, Jiayan Li, Jiami Gong, et al. "Evolving SARS-CoV-2 Vaccines: From Current Solutions to Broad-Spectrum Protection." Vaccines 13, no. 6 (2025): 635. https://doi.org/10.3390/vaccines13060635.
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The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine efficacy, necessitating ongoing surveillance and vaccine adaptation. Current SARS-CoV-2 vaccines, including inactivated, live-attenuated, viral vector, protein subunit, virus-like particle, and nucleic acid vaccines, face challenges due to the immune evasion strategies of emerging variants. Moreover, other sarbecoviruses, such as SARS-CoV-1 and SARS-related coronaviruses (SARSr-CoVs) pose a potential risk for future outbreaks. Thus, developing vaccines capable of countering emerging SARS-CoV-2 variants and providing broad protection against multiple sarbecoviruses is imperative. Several innovative vaccine platforms are being investigated to elicit broad-spectrum neutralizing antibody responses, offering protection against both current SARS-CoV-2 variants and other sarbecoviruses. This review presents an updated overview of the key target antigens and therapeutic strategies employed in current SARS-CoV-2 vaccines. Additionally, we summarize ongoing approaches for the development of vaccines targeting infectious sarbecoviruses.
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Julia San Miguel Rodríguez, Julita Rodríguez Barbero, Angel San Miguel Hernández, Angel San Miguel Rodríguez, and María San Miguel Rodríguez. "Vaccines against SARS-COV-2." GSC Advanced Research and Reviews 8, no. 2 (2021): 045–57. http://dx.doi.org/10.30574/gscarr.2021.8.2.0143.
Full textAbstract:
Vaccines against Covid-19 were developed on the basis of protein S, before it had the mutations identified in these variants. Although research conducted so far is less effective against variants and continues to offer protection against severe forms of Covid-19, further research is ongoing. WHO is working with every country in the world to help coordinate the key stages of this vaccine manufacturing and development process. In particular, to facilitate equitable access for all countries to vaccines against Covid-19 and that they are safe and effective for the billions of people who need them.
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Azad, Taha, Ragunath Singaravelu, Mathieu J. F. Crupi, et al. "Implications for SARS-CoV-2 Vaccine Design: Fusion of Spike Glycoprotein Transmembrane Domain to Receptor-Binding Domain Induces Trimerization." Membranes 10, no. 9 (2020): 215. http://dx.doi.org/10.3390/membranes10090215.
Full textAbstract:
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presents an urgent need for an effective vaccine. Molecular characterization of SARS-CoV-2 is critical to the development of effective vaccine and therapeutic strategies. In the present study, we show that the fusion of the SARS-CoV-2 spike protein receptor-binding domain to its transmembrane domain is sufficient to mediate trimerization. Our findings may have implications for vaccine development and therapeutic drug design strategies targeting spike trimerization. As global efforts for developing SARS-CoV-2 vaccines are rapidly underway, we believe this observation is an important consideration for identifying crucial epitopes of SARS-CoV-2.
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Goel, Rishi R., Sokratis A. Apostolidis, Mark M. Painter, et al. "Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination." Science Immunology 6, no. 58 (2021): eabi6950. http://dx.doi.org/10.1126/sciimmunol.abi6950.
Full textAbstract:
Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.
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Bijukchhe, Sanjeev M., Peter J. O'Reilly, Katherine Theiss-Nyland, et al. "COVID-19 vaccine effectiveness and variants in Nepal: study protocol for a test-negative case–control study with SARS-CoV-2 genetic sequencing." BMJ Open 13, no. 4 (2023): e068334. http://dx.doi.org/10.1136/bmjopen-2022-068334.
Full textAbstract:
IntroductionInactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants.Methods and analysisThis is a hospital-based, prospective test-negative case–control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts.Ethics and disseminationEthical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.
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Head, Katharine J., Monica L. Kasting, Lynne A. Sturm, Jane A. Hartsock, and Gregory D. Zimet. "A National Survey Assessing SARS-CoV-2 Vaccination Intentions: Implications for Future Public Health Communication Efforts." Science Communication 42, no. 5 (2020): 698–723. http://dx.doi.org/10.1177/1075547020960463.
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With SARS-CoV-2 vaccines under development, research is needed to assess intention to vaccinate. We conducted a survey ( N = 3,159) with U.S. adults in May 2020 assessing SARS-CoV-2 vaccine intentions, intentions with a provider recommendation, and sociodemographic and psychosocial variables. Participants had high SARS-CoV-2 vaccine intentions ( M = 5.23/7-point scale), which increased significantly with a provider recommendation ( M = 5.47). Hierarchical linear regression showed that less education and working in health care were associated with lower intent, and liberal political views, altruism, and COVID-19-related health beliefs were associated with higher intent. This work can inform interventions to increase vaccine uptake, ultimately reducing COVID-19-related morbidity and mortality.
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Earar, Kamel, Vania Atudorei, Isteqlal Sami Nazmi Mahmoud, et al. "COVID-19 Vaccine: A Global Race." Revista de Chimie 71, no. 6 (2020): 327–31. http://dx.doi.org/10.37358/rc.20.6.8199.
Full textAbstract:
The emergence of the new coronavirus SARS-CoV-2, at the end of 2019, triggered the worst pandemic of the last century, called COVID-19. Unlike SARS-CoV-1, which developed as an epidemic in 1996 but was limited to Asia, the new SARS -CoV-2 spread rapidly to millions of people worldwide, with a high mortality rate. Deciphering the structure of the viral S and SARS-CoV genome-2 allowed the identification of targets for vaccination, the most important being the viral protein S. The development of -COVID-19 vaccines is based on use innovative biotechnologies, some even experimental. Experience in vaccines SARS-CoV-1-MERS-CoV and may be useful for designing bad vaccine by emerging virus of SARS-CoV-2. Developing a vaccine anti-COVID-19 efficient, safe and accessible in the shortest possible time, remains the biggest challenge overall, in the race to limit pandemic today.
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Kotarya, Bharti, Abhishek Pandeya, Raj Kumar Khalko, et al. "PROSPECTS OF SARS-CoV-2 VACCINES AND THEIR LANDSCAPE." Journal of Experimental Biology and Agricultural Sciences 8, Spl-1-SARS-CoV-2 (2020): S246—S263. http://dx.doi.org/10.18006/2020.8(spl-1-sars-cov-2).s246.s263.
Full textAbstract:
Severe Acute Respiratory Syndrome Corona Virus -2 (SARS-CoV-2), puzzled the whole world with its diverse, unique clinical spectrum, and unprecedented transmission dynamics. The disease caused by this virus is named as Coronavirus disease-19 (COVID-19), reported first time in Wuhan, China, in December 2019. It had spread to almost all countries of the world disrupting the health and economy of many countries. It was the recent zoonotic spillover disease reported in humans from the Coronavirus group, without proper medicine and non-existence of prior immunity, this disease posed a challenge to both the scientific and medical fraternity. The search for safe, effective drugs to treat the disease and vaccines against the causative agent SARS- CoV-2 had begun all over the world with public and private partnerships. Many countries are part of the solidarity trail for identifying the effective drugs, clinical trials and vaccines for this global pandemic. Here in this review, we are focussing on the different vaccine production platforms being used in the preparation of vaccines against SARS-CoV-2, their current status and prospects. Vaccine production technology significantly advanced in recent times by imbibing the cutting edge technologies such as nucleic acid based technologies such as DNA/RNA/Codon deoptimization and availability of safe and effective viral vectors produced through rDNA technology. The availability of complete genome sequence of SARS-CoV-2, geared up for the production of vaccine candidates based on these new vaccine production platforms, and in a record time of 4-5 months, these vaccine candidates entered in human clinical trials for the evaluation of safety and efficacy. Prior knowledge on SARS and MERS-CoV’s structural and genomic features, vaccine production platforms used in making vaccines against them greatly augmented in the SARS-CoV-2 vaccine efforts. As per World Health Organization (WHO) a total of202 vaccine candidates are under developing for SARS-CoV-2, among them 47 entered in clinical trials and 156 are in the preclinical stage. These vaccines are prepared by an amalgamation of both new and old traditional vaccine production platforms such as nucleic acid base platforms, inactivated, live attenuated, recombinant viral vectors, protein and peptide-based vaccines. The success of these vaccine candidates lies in the generation of effective immune response for SARS-CoV-2 across all age groups and people with co-morbidities. We briefly summarize the different strategies of SARS-CoV-2 vaccine production and their prospects with an emphasis on different routes of administration and added a basic mathematical model depicting the importance of vaccination for any pandemic.
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Veljkovic, Veljko, Vladimir Perovic, and Slobodan Paessler. "Prediction of the effectiveness of COVID-19 vaccine candidates." F1000Research 9 (May 14, 2020): 365. http://dx.doi.org/10.12688/f1000research.23865.1.
Full textAbstract:
A safe and effective vaccine is urgently needed to bring the current SARS-CoV-2 pandemic under control. The spike protein (SP) of SARS-CoV-2 represents the principal target for most vaccines currently under development. This protein is highly conserved indicating that vaccine based on this antigen will be efficient against all currently circulating SARS-CoV-2 strains. The present analysis of SP suggests that mutation D614G could significantly decrease the effectiveness of the COVID-19 vaccine through modulation of the interaction between SARS-CoV-2 and its principal receptor ACE2.
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Waickman, Adam T., Joseph Lu, Corey Chase, et al. "Systemic Cancer Therapy Does Not Significantly Impact Early Vaccine-Elicited SARS-CoV-2 Immunity in Patients with Solid Tumors." Vaccines 10, no. 5 (2022): 738. http://dx.doi.org/10.3390/vaccines10050738.
Full textAbstract:
mRNA vaccines have been shown to be safe and effective in individuals with cancer. It is unclear, however, if systemic anti-cancer therapy impacts the coordinated cellular and humoral immune responses elicited by SARS-CoV-2 mRNA vaccines. To fill this knowledge gap, we assessed SARS-CoV-2 mRNA vaccine-elicited immunity in a cohort of patients with advanced solid tumors either under observation or receiving systemic anti-cancer therapy. This analysis revealed that SARS-CoV-2 mRNA vaccine-elicited cellular and humoral immunity was not significantly different in individuals with cancer receiving systemic anti-cancer therapy relative to individuals under observation. Furthermore, even though some patients exhibited suboptimal antibody titers after vaccination, SARS-CoV-2 specific cellular immune responses were still detected. These data suggest that antibody titers offer an incomplete picture of vaccine-elicited SARS-CoV-2 immunity in cancer patients undergoing active systemic anti-cancer therapy, and that vaccine-elicited cellular immunity exists even in the absence of significant quantities of SARS-CoV-2 specific antibodies.
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Said, Elias A., Afnan Al-Rubkhi, Sanjay Jaju, et al. "Association of the Magnitude of Anti-SARS-CoV-2 Vaccine Side Effects with Sex, Allergy History, Chronic Diseases, Medication Intake, and SARS-CoV-2 Infection." Vaccines 12, no. 1 (2024): 104. http://dx.doi.org/10.3390/vaccines12010104.
Full textAbstract:
Vaccination provides the best protection against the increasing infections of SARS-CoV-2. The magnitude and type of anti-SARS-CoV-2 vaccine side effects (SEs) depend on parameters that are not fully understood. In this cross-sectional study, the associations between different anti-SARS-CoV-2 vaccine SEs and age, sex, the presence of chronic diseases, medication intake, history of allergies, and infections with SARS-CoV-2 were investigated. Our survey used the Google platform and had 866 participants, contacted through e-mails, social media and chain referral sampling (margin of error ≈ 4.38%, 99% confidence). More than 99% of the participants received the BNT162b2 and ChAdOx1-S vaccines. Being female, having chronic diseases, taking medicines routinely and the presence of a SARS-CoV-2 infection (p < 0.05) were associated with strong SEs after the BNT162b2 vaccine second dose. Having a history of allergies and a female sex (p < 0.01) were associated with strong SEs after the ChAdOx1-S vaccine second dose. Furthermore, the results reveal, for the first time, the associations between having a history of allergies, chronic diseases, medication usage, and SEs of a strong magnitude for the BNT162b2 and ChAdOx1-S vaccines. Additionally, this study supports the association of the female sex and infection with SARS-CoV-2 with an increased potential of developing stronger SEs with certain anti-SARS-CoV-2 vaccines.
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Bommireddy, Ramireddy, Shannon Stone, Noopur Bhatnagar, et al. "Influenza Virus-like Particle-Based Hybrid Vaccine Containing RBD Induces Immunity against Influenza and SARS-CoV-2 Viruses." Vaccines 10, no. 6 (2022): 944. http://dx.doi.org/10.3390/vaccines10060944.
Full textAbstract:
Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since millions of people are exposed to influenza virus and SARS-CoV-2, it is of great interest to develop a two-in-one vaccine that will be able to protect against infection of both viruses. We have developed a hybrid vaccine for SARS-CoV-2 and influenza viruses using influenza virus-like particles (VLP) incorporated by protein transfer with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 RBD fused to GM-CSF as an adjuvant. GPI-RBD-GM-CSF fusion protein was expressed in CHO-S cells, purified and incorporated onto influenza VLPs to develop the hybrid vaccine. Our results show that the hybrid vaccine induced a strong antibody response and protected mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having significantly lower lung viral titers compared to naive mice. These results suggest that a hybrid vaccine strategy is a promising approach for developing multivalent vaccines to prevent influenza A and SARS-CoV-2 infections.
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Hong, So-Hee, Hanseul Oh, Yong Wook Park, et al. "Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates." Science Advances 7, no. 22 (2021): eabg7156. http://dx.doi.org/10.1126/sciadv.abg7156.
Full textAbstract:
Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.
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Bommireddy, Ramireddy, Shannon Stone, Noopur Bhatnagar, et al. "Influenza virus-like particle-based hybrid vaccine containing RBD induces immunity against influenza and SARS-CoV-2 viruses." Journal of Immunology 208, no. 1_Supplement (2022): 64.01. http://dx.doi.org/10.4049/jimmunol.208.supp.64.01.
Full textAbstract:
Abstract Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the influence of immunity against other vaccinations on the durability and efficacy of the immune response against SARS-CoV-2 is still unknown in settings where vaccines against other viruses need to be administered simultaneously. This will be an important factor in developing multivalent vaccines against seasonal viruses. We have developed a hybrid vaccine for SARS-CoV-2 and influenza viruses using influenza virus-like particles (VLP) incorporated with glycosylphosphatidylinositol (GPI)-anchored Spike RBD of SARS-CoV-2 fused to GM-CSF as an adjuvant. GPI-anchored fusion protein of GM-CSF and the SARS-CoV-2 S1 RBD was expressed in CHO-S cells, purified by immunoaffinity chromatography and incorporated onto influenza VLPs by protein transfer to make a hybrid VLP vaccine. The efficacy of the hybrid VLP vaccine was tested against both SARS-CoV-2 and influenza A/PR8 viruses in a mouse model. Our results show that the hybrid vaccine induced a strong antibody response and protected the mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having less body weight loss and significantly lower lung viral titers compared to control mice. These results suggest that the hybrid vaccine is a promising candidate for preventing influenza A and SARS-CoV-2 infections. This work was supported by NIH/NIAID (SBIR Contract# 75N93019C00017 Amendment to Pack/Ramachandiran), and Intel Corporation for the Intel COVID-19 Global Technology Response Initiative grant.
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Satoru, Nakamura Kawatana Medical Center Japan. "Current Research Status of SARS-CoV-2 as a Pathogen of COVID-19." Journal of Health and Medical Sciences 3, no. 2 (2020): 184. https://doi.org/10.31014/aior.1994.03.02.113.
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COVID-19 was first identified in an outbreak in Wuhan, China, in December 2019. COVID-19 is defined as Corona Virus Infectious Disease 2019, and it’s caused by SARS (severe acute respiratory syndrome)-CoV (coronavirus)-2. This article shows the current research status on SARS-CoV-2.
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Wiest, Nathaniel E., Gretchen S. Johns, and Eric Edwards. "A Case of Acute Pulmonary Embolus after mRNA SARS-CoV-2 Immunization." Vaccines 9, no. 8 (2021): 903. http://dx.doi.org/10.3390/vaccines9080903.
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Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a critical strategy to overcome the COVID-19 pandemic. Multiple SARS-CoV-2 vaccines have been developed in a rapid timeframe to combat the pandemic. While generally safe and effective, rare cases of venous thromboembolism (VTE) have been reported after two adenovirus-based vaccines, the AstraZeneca ChAdOx1 nCoV-19 vaccine and the Janssen Ad.26.COV2.S vaccine, as well as after the Pfizer-BioNTech BNT162b2 mRNA vaccine. Here, we present the case of a patient who developed acute pulmonary emboli (PE) shortly after his second dose of the Moderna mRNA-1273 SARS-CoV-2 vaccine. We report the results of an extensive thrombophilia workup that was normal except for the identification of positive lupus anticoagulant (LA) signals. It is our goal to contribute to the body of knowledge regarding SARS-CoV-2 vaccines and encourage vaccine adverse event reporting so that clinicians can have a full appreciation and awareness of the possible adverse events related to these critical vaccines.
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Veljkovic, Veljko, Vladimir Perovic, Isabelle Chambers, and Slobodan Paessler. "Evolution of SARS-CoV-2 virus and assessment of the effectiveness of COVID-19 vaccine." F1000Research 10 (January 18, 2021): 28. http://dx.doi.org/10.12688/f1000research.28215.1.
Full textAbstract:
A safe and effective vaccine is urgently needed to bring the current SARS-CoV-2 pandemic under control. The spike protein (SP) of SARS-CoV-2 represents the principal target for most vaccines currently under development. Despite the presence of a CoV proof-reading function in viral replication, SP protein from SARS-CoV still extensively mutates, which might have an impact on current and future vaccine development. Here, we present analysis of more than 1600 SP unique variants suggesting that vaccine candidates based on the Wuhan-Hu-1 reference strain would be effective against most of currently circulated SARS-CoV-2 viruses, but that further monitoring of the evolution of this virus is important for identification of other mutations, which could affect the effectiveness of vaccines.
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Currier, Arthur W., Madeline C. Jeshurin, and Valerie B. Sampson. "SARS-CoV-2 Targets and COVID-19 Vaccines." COVID 1, no. 3 (2021): 608–21. http://dx.doi.org/10.3390/covid1030051.
Full textAbstract:
Coronavirus disease-2019 (COVID-19) vaccines are being used across the globe to reduce the risk of developing COVID-19, stop the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and end the pandemic. To address this, a massive global effort is underway for development of COVID-19 vaccines. As of September 2021, the World Health Organization (WHO) has documented 331 COVID-19 vaccine candidates, and 107 are in clinical evaluation, with 8 in Phase IV and 30 in Phase III clinical trials (WHO; COVID-19 vaccine tracker). At least 13 different vaccines are being issued for emergency use authorization. Specifically, the goal is to produce protective immunity to SARS-CoV-2 infection by stimulating an immune response to either the whole virus, viral protein, or nucleic acid products. The spike (S) proteins of SARS-CoV-2 that give the characteristic “corona” appearance of this family of viruses has emerged as an effective target for vaccines. Other viral candidates that are being developed also aim to produce immunity for COVID-19. In this review, we describe the different vaccine platforms, target candidates for vaccines, and their progress in COVID-19 vaccine development. This is critical since newly discovered SARS-CoV-2 variants of interest require understanding of how vaccines may provide the most effective long-term protection against infection.
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Clever, Sabrina, Leonard Limpinsel, Christian Meyer zu Natrup, et al. "Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection." Viruses 16, no. 3 (2024): 417. http://dx.doi.org/10.3390/v16030417.
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The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens.
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Xu, Kangwei, Jing Li, Xu Lu, et al. "The Immunogenicity of CpG, MF59-like, and Alum Adjuvant Delta Strain Inactivated SARS-CoV-2 Vaccines in Mice." Vaccines 12, no. 1 (2024): 60. http://dx.doi.org/10.3390/vaccines12010060.
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The continuous evolution and mutation of SARS-CoV-2 have highlighted the need for more effective vaccines. In this study, CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines were prepared, and the immunogenicity of these vaccines in mice was evaluated. The Delta + MF59-like vaccine group produced the highest levels of S- and RBD-binding antibodies and live Delta virus neutralization levels after one shot of immunization, while mice in the Delta + Alum vaccine group had the highest levels of these antibodies after two doses, and the Delta + MF59-like and Delta + Alum vaccine groups produced high levels of cross-neutralization antibodies against prototype, Beta, and Gamma strain SARS-CoV-2 viruses. There was no significant decrease in neutralizing antibody levels in any vaccine group during the observation period. CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines excited different antibody subtypes compared with unadjuvanted vaccines; the Delta + CpG vaccine group had a higher proportion of IgG2b antibodies, indicating bias towards Th1 immunity. The proportions of IgG1 and IgG2b in the Delta + MF59-like vaccine group were similar to those of the unadjuvanted vaccine. However, the Delta + Alum vaccine group had a higher proportion of IgG1 antibodies, indicating bias towards Th2 immunity. Antigen-specific cytokine secretion CD4/8+ T cells were analyzed. In conclusion, the results of this study show differences in the immune efficacy of CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines in mice, which have significant implications for the selection strategy for vaccine adjuvants.
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Houston, Stephanie. "SARS-CoV-2 mucosal vaccine." Nature Immunology 24, no. 1 (2023): 1. http://dx.doi.org/10.1038/s41590-022-01405-w.
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Cao, Han, Shengran Yang, Yunfei Wang, et al. "An Established Th2-Oriented Response to an Alum-Adjuvanted SARS-CoV-2 Subunit Vaccine Is Not Reversible by Sequential Immunization with Nucleic Acid-Adjuvanted Th1-Oriented Subunit Vaccines." Vaccines 9, no. 11 (2021): 1261. http://dx.doi.org/10.3390/vaccines9111261.
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A recently reported parallel preclinical study between a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine and an inactivated SARS-CoV-2 vaccine adjuvanted with alum showed pulmonary immunopathology typical of eosinophil accumulation in a mouse pneumonia model for the latter, which implied a potential role of cellular immunity in the difference in the protection rate between these two forms of vaccines. For those who have been vaccinated with alum-adjuvanted subunit or inactivated SARS-CoV-2 vaccines, whether the Th2 responses that have been established and the absence of induced cellular immunity could be changed is an open question. Using two heterologous boosts with Th1-oriented CpG ODN-adjuvanted S1-based SARS-CoV-2 subunit vaccines for mice that were primed with two doses of Th2-oriented alum-adjuvanted S1-based SARS-CoV-2 subunit vaccines, we demonstrated that established Th2 orientation could not be reversed to Th1 orientation and that no cellular immunity was induced, which should have been induced if the boosting vaccines were used as the prime vaccines. These results remind us that if widely administered alum-adjuvanted SARS-CoV-2 vaccines cannot overcome the challenge of coronavirus disease 2019 (COVID-19) and that if cellular immunity is important for the efficacy of SARS-CoV-2 vaccines in the future, the choice of more powerful heterologous boosting vaccine forms that can induce cellular immunity should be considered very carefully before application.
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Enticott, Joanne, Jaskirath Singh Gill, Simon L. Bacon, et al. "Attitudes towards vaccines and intention to vaccinate against COVID-19: a cross-sectional analysis—implications for public health communications in Australia." BMJ Open 12, no. 1 (2022): e057127. http://dx.doi.org/10.1136/bmjopen-2021-057127.
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ObjectiveTo examine SARS-CoV-2 vaccine confidence, attitudes and intentions in Australian adults as part of the iCARE Study.Design and settingCross-sectional online survey conducted when free COVID-19 vaccinations first became available in Australia in February 2021.ParticipantsTotal of 1166 Australians from general population aged 18–90 years (mean 52, SD of 19).Main outcome measuresPrimary outcome: responses to question ‘If a vaccine for COVID-19 were available today, what is the likelihood that you would get vaccinated?’.Secondary outcome: analyses of putative drivers of uptake, including vaccine confidence, socioeconomic status and sources of trust, derived from multiple survey questions.ResultsSeventy-eight per cent reported being likely to receive a SARS-CoV-2 vaccine. Higher SARS-CoV-2 vaccine intentions were associated with: increasing age (OR: 2.01 (95% CI 1.77 to 2.77)), being male (1.37 (95% CI 1.08 to 1.72)), residing in least disadvantaged area quintile (2.27 (95% CI 1.53 to 3.37)) and a self-perceived high risk of getting COVID-19 (1.52 (95% CI 1.08 to 2.14)). However, 72% did not believe they were at a high risk of getting COVID-19. Findings regarding vaccines in general were similar except there were no sex differences. For both the SARS-CoV-2 vaccine and vaccines in general, there were no differences in intentions to vaccinate as a function of education level, perceived income level and rurality. Knowing that the vaccine is safe and effective and that getting vaccinated will protect others, trusting the company that made it and vaccination recommended by a doctor were reported to influence a large proportion of the study cohort to uptake the SARS-CoV-2 vaccine. Seventy-eight per cent reported the intent to continue engaging in virus-protecting behaviours (mask wearing, social distancing, etc) postvaccine.ConclusionsMost Australians are likely to receive a SARS-CoV-2 vaccine. Key influencing factors identified (eg, knowing vaccine is safe and effective, and doctor’s recommendation to get vaccinated) can inform public health messaging to enhance vaccination rates.
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Heo, Chang-Kyu, Won-Hee Lim, Ki-Beom Moon, et al. "S2 Peptide-Conjugated SARS-CoV-2 Virus-like Particles Provide Broad Protection against SARS-CoV-2 Variants of Concern." Vaccines 12, no. 6 (2024): 676. http://dx.doi.org/10.3390/vaccines12060676.
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Approved COVID-19 vaccines primarily induce neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the emergence of variants of concern with RBD mutations poses challenges to vaccine efficacy. This study aimed to design a next-generation vaccine that provides broader protection against diverse coronaviruses, focusing on glycan-free S2 peptides as vaccine candidates to overcome the low immunogenicity of the S2 domain due to the N-linked glycans on the S antigen stalk, which can mask S2 antibody responses. Glycan-free S2 peptides were synthesized and attached to SARS-CoV-2 virus-like particles (VLPs) lacking the S antigen. Humoral and cellular immune responses were analyzed after the second booster immunization in BALB/c mice. Enzyme-linked immunosorbent assay revealed the reactivity of sera against SARS-CoV-2 variants, and pseudovirus neutralization assay confirmed neutralizing activities. Among the S2 peptide-conjugated VLPs, the S2.3 (N1135-K1157) and S2.5 (A1174-L1193) peptide–VLP conjugates effectively induced S2-specific serum immunoglobulins. These antisera showed high reactivity against SARS-CoV-2 variant S proteins and effectively inhibited pseudoviral infections. S2 peptide-conjugated VLPs activated SARS-CoV-2 VLP-specific T-cells. The SARS-CoV-2 vaccine incorporating conserved S2 peptides and CoV-2 VLPs shows promise as a universal vaccine capable of generating neutralizing antibodies and T-cell responses against SARS-CoV-2 variants.
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Samaranayake, Lakshman. "Current COVID-19 vaccine epidemiology and dentistry." Dental Update 48, no. 10 (2021): 881–86. http://dx.doi.org/10.12968/denu.2021.48.10.881.
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The coronavirus disease 2019 (COVID-19) vaccine story is continuously unfolding. Since our previous COVID-19 commentaries, much new information has transpired on the subject, and here we revisit this topic, which has practical implications for all stakeholders in dentistry, as well as the public. This article, on current vaccine epidemiology, provides an account of why vaccines fail in general, and the particular concerns in relation to the new Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related ‘variants of concern’. Issues related to vaccine failure are fundamentally dichotomous in nature, appertaining either to the vaccine strain (type) per se, and/or the numerous endogenous factors of the vaccine recipient/vaccinee. Societal factors such as vaccine hesitancy and its impact on herd immunity appear to overarch the long-term goal of total or partial global suppression of SARS-CoV-2, and its eventual endemicity. CPD/Clinical Relevance: To describe the reasons for the failure of currently administered COVID-19 vaccines, particularly in relation to the advent of the SARS-CoV-2 ‘variants of concern’, and discuss implications for clinical dental practice.
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Oğuz, Seda Hanife, Süleyman Nahit Şendur, Burçin Gönül İremli, Alper Gürlek, Tomris Erbas, and Uğur Ünlütürk. "SARS-CoV-2 Vaccine–induced Thyroiditis: Safety of Revaccinations and Clinical Follow-up." Journal of Clinical Endocrinology & Metabolism 107, no. 5 (2022): e1823-e1834. http://dx.doi.org/10.1210/clinem/dgac049.
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Abstract Context The number of reported cases with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine–induced subacute thyroiditis (SAT) and Graves’ disease (GD) is growing. However, active debate continues about managing such side effects and the safety of repeat or booster doses of the vaccines in such cases. Objectives This study aims to present long-term clinical follow-up of SARS-CoV-2 vaccine–induced SAT or GD cases and provide data regarding the safety of revaccinations. Methods Patients diagnosed with SARS-CoV-2 vaccine–induced SAT or GD were included. Data regarding the long-term clinical follow-up of SARS-CoV-2 vaccine–induced SAT and GD cases and outcomes of repeat or booster SARS-CoV-2 vaccinations were documented. The literature, including cases of SARS-CoV-2 vaccine–induced SAT or GD, was reviewed. Results Fifteen patients with SARS-CoV-2 vaccine–induced SAT and 4 with GD were included. Pfizer/BioNTech COVID-19 vaccine (BNT162b2) was associated with symptoms in a majority of cases with SAT and all with GD. Median time from vaccination to symptom onset was 7 and 11.5 days, respectively, while 7 and 2 patients required medical treatment in SAT and GD groups, respectively. Remission was documented in 10 SAT patients, with a median time to remission of 11.5 weeks. No exacerbation/recurrence of SAT occurred in 7 of 9 patients who received a repeat vaccination dose, while symptoms of SAT worsened following the second vaccination in 2 cases. None of the patients experienced severe side effects that could be associated with revaccinations. Conclusions Revaccinations appear to be safe in patients with SARS-CoV-2 vaccine–induced SAT cases, while more evidence is needed regarding SARS-CoV-2 vaccine–induced GD.
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Mikhail, NASSER, and Soma Wali. "Graves’ disease Induced by Sars-Cov-2 Vaccination." Journal of Clinical Research and Reports 11, no. 2 (2022): 01–05. http://dx.doi.org/10.31579/2690-1919/247.
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Background: Several cases of Graves’ disease were recently reported in individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To determine characteristics and patterns of Graves’ disease occurring following SARS-CoBV-2 vaccination. Methods: PubMed search up to March 31st, 2022. Search terms are Graves’ disease, SARS-Cov-2, vaccine, COVID-19. Case reports, case series, review articles and pertinent in vitro studies are reviewed. Results: Review of literature revealed 28 cases (19 women) of new onset and 5 cases (4 women) of relapses of Graves’ disease after receiving different types of vaccines against coronavirus disease 2019 (COVID-19). Onset of hyperthyroid symptoms started 2-60 days after vaccination and occurred more frequently after the first vaccine dose (n=13) than after the second dose (n=5). In 70% of cases (23 of 33), the implicated agent was the m-RNA based vaccine of Pfizer-BioNtech. Severity of Graves’ disease symptoms was generally moderate and controlled by anti-thyroid medications (mainly methimazole) and beta-adrenergic blockers. The course of Graves’ disease is unclear as patients are still receiving therapy. No specific risk factors could be defined that may increase predisposition to the COVID-19 vaccine-induced Graves’ disease. Mechanisms of development of Graves’ disease after COVID-19 vaccination are unclear but may be related to the phenomena of molecular mimicry or autoimmune/inflammatory syndrome by adjuvants (ASIA). Conclusions: The timing of onset of symptoms of Graves’ disease in relation to the administration of COVID-19 vaccine strongly suggests a causal relationship. Physicians should be aware of the occurrence of this uncommon adverse effect.
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Dangi, Tanushree, Nicole M. Palacio, Sarah Sanchez, and Pablo Penaloza-MacMaster. "Characterization of cross-reactive immunity following coronavirus vaccination or natural infection." Journal of Immunology 206, no. 1_Supplement (2021): 103.13. http://dx.doi.org/10.4049/jimmunol.206.supp.103.13.
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Abstract SARS-CoV-2 has infected more than 100 million people worldwide. Several vaccine candidates have been deployed under emergency use authorization, but it is unclear whether a coronavirus (CoV) vaccine can protect against other CoV. To investigate this proof-of-concept, we evaluated cross-reactive immunity following vaccination with a modified vaccinia Ankara expressing SARS-CoV-1 spike protein. We first vaccinated C57BL/6 mice intramuscularly and then measured heterologous antibodies (SARS-CoV-2, OC43 and mouse hepatitis virus, MHV) by ELISA. Interestingly, the SARS-CoV-1 vaccine elicited cross-reactive antibodies that recognize these other CoV. Sera from mice immunized with the SARS-CoV-1 vaccine neutralized SARS-CoV-2 pseudovirus in vitro (5-fold greater than control naïve sera; p=0.007), and transfer of these immune sera into naïve mice provided partial protection after heterologous challenges. Similar cross-reactivity was observed following immunization with a SARS-CoV-2 vaccine, and we mapped a conserved CD8 T cell epitope in both SARS-CoV-1 and CoV-2 spike protein, allowing us to develop an MHC tetramer to track this cross-reactive response. Finally, we interrogated whether a CoV infection could elicit cross-reactive immunity. We show that an OC43 infection generated cross-reactive antibodies against SARS-CoV-2, OC43 and MHV, and conferred partial protection against MHV challenge. In summary, our findings demonstrate that cross-reactive immunity can be elicited by vaccination, providing a framework for the rational design of universal CoV vaccines. Moreover, these data suggest that prior infection with endemic CoV may provide partial protection against other CoVs.