Journal articles: 'Vaccine candidate genes'

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Huang, Claire Y. H., Siritorn Butrapet, Dennis J. Pierro, Gwong-Jen J. Chang, Ann R. Hunt, Natth Bhamarapravati, Duane J. Gubler, and Richard M. Kinney. "Chimeric Dengue Type 2 (Vaccine Strain PDK-53)/Dengue Type 1 Virus as a Potential Candidate Dengue Type 1 Virus Vaccine." Journal of Virology 74, no. 7 (April 1, 2000): 3020–28. http://dx.doi.org/10.1128/jvi.74.7.3020-3028.2000.

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ABSTRACT We constructed chimeric dengue type 2/type 1 (DEN-2/DEN-1) viruses containing the nonstructural genes of DEN-2 16681 virus or its vaccine derivative, strain PDK-53, and the structural genes (encoding capsid protein, premembrane protein, and envelope glycoprotein) of DEN-1 16007 virus or its vaccine derivative, strain PDK-13. We previously reported that attenuation markers of DEN-2 PDK-53 virus were encoded by genetic loci located outside the structural gene region of the PDK-53 virus genome. Chimeric viruses containing the nonstructural genes of DEN-2 PDK-53 virus and the structural genes of the parental DEN-1 16007 virus retained the attenuation markers of small plaque size and temperature sensitivity in LLC-MK2 cells, less efficient replication in C6/36 cells, and attenuation for mice. These chimeric viruses elicited higher mouse neutralizing antibody titers against DEN-1 virus than did the candidate DEN-1 PDK-13 vaccine virus or chimeric DEN-2/DEN-1 viruses containing the structural genes of the PDK-13 virus. Mutations in the envelope protein of DEN-1 PDK-13 virus affected in vitro phenotype and immunogenicity in mice. The current PDK-13 vaccine is the least efficient of the four Mahidol candidate DEN virus vaccines in human trials. The chimeric DEN-2/DEN-1 virus might be a potential DEN-1 virus vaccine candidate. This study indicated that the infectious clones derived from the candidate DEN-2 PDK-53 vaccine are promising attenuated vectors for development of chimeric flavivirus vaccines.

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Maksyutov, R. A., S. N. Yakubitskyi, I. V. Kolosova, and S. N. Shchelkunov. "Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections." Acta Naturae 9, no. 2 (June 15, 2017): 88–93. http://dx.doi.org/10.32607/20758251-2017-9-2-88-93.

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The lack of immunity to the variola virus in the population, increasingly more frequent cases of human orthopoxvirus infection, and increased risk of the use of the variola virus (VARV) as a bioterrorism agent call for the development of modern, safe vaccines against orthopoxvirus infections. We previously developed a polyvalent DNA vaccine based on five VARV antigens and an attenuated variant of the vaccinia virus (VACV) with targeted deletion of six genes (VAC6). Independent experiments demonstrated that triple immunization with a DNA vaccine and double immunization with VAC6 provide protection to mice against a lethal dose (10 LD50) of the ectromelia virus (ECTV), which is highly pathogenic for mice. The present work was aimed at comparing the immunity to smallpox generated by various immunization protocols using the DNA vaccine and VAC6. It has been established that immunization of mice with a polyvalent DNA vaccine, followed by boosting with recombinant VAC6, as well as double immunization with VAC6, induces production of VACV-neutralizing antibodies and provides protection to mice against a 150 LD50 dose of ECTV. The proposed immunization protocols can be used to develop safe vaccination strategies against smallpox and other human orthopoxvirus infections.

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Adler, Ben, Dieter Bulach, Jing Chung, Stephen Doughty, Meredith Hunt, Kumar Rajakumar, Maria Serrano, Angela van Zanden, Yamei Zhang, and Carmel Ruffolo. "Candidate vaccine antigens and genes in Pasteurella multocida." Journal of Biotechnology 73, no. 2-3 (August 1999): 83–90. http://dx.doi.org/10.1016/s0168-1656(99)00111-x.

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Võ, Tuấn-Cường, Haung Naw, Rochelle A. Flores, Hương-Giang Lê, Jung-Mi Kang, Won-Gi Yoo, Woo-Hyun Kim, Wongi Min, and Byoung-Kuk Na. "Genetic Diversity of Microneme Protein 2 and Surface Antigen 1 of Eimeria tenella." Genes 12, no. 9 (September 15, 2021): 1418. http://dx.doi.org/10.3390/genes12091418.

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Avian coccidiosis is a disease caused by members of the genus Eimeria. Huge economic losses incurred by the global poultry industry due to coccidiosis have increased the need for cost-effective and easily available recombinant vaccines. Microneme protein 2 (MIC2) and surface antigen 1 (SAG1) of E. tenella have been recognised as potential vaccine candidates. However, the genetic diversity of the antigens in field isolates, which affects vaccine efficacy, has yet to be largely investigated. Here, we analysed genetic diversity and natural selection of etmic2 and etsag1 in Korean E. tenella isolates. Both genes exhibited low levels of genetic diversity in Korean isolates. However, the two genes showed different patterns of nucleotide diversity and amino acid polymorphism involving the E. tenella isolates obtained from different countries including China and India. These results underscore the need to investigate the genetic diversity of the vaccine candidate antigens and warrant monitoring of genetic heterogeneity and evolutionary aspects of the genes in larger numbers of E. tenella field isolates from different geographical areas to design effective coccidial vaccines.

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Burgers, Wendy A., Gerald K. Chege, Tracey L. Müller, Joanne H. van Harmelen, Greg Khoury, Enid G. Shephard, Clive M. Gray, Carolyn Williamson, and Anna-Lise Williamson. "Broad, high-magnitude and multifunctional CD4+ and CD8+ T-cell responses elicited by a DNA and modified vaccinia Ankara vaccine containing human immunodeficiency virus type 1 subtype C genes in baboons." Journal of General Virology 90, no. 2 (February 1, 2009): 468–80. http://dx.doi.org/10.1099/vir.0.004614-0.

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Candidate human immunodeficiency virus (HIV) vaccine regimens based on DNA boosted with recombinant modified vaccinia Ankara (MVA) have been in development for some time, and there is evidence for improved immunogenicity of newly developed constructs. This study describes immune responses to candidate DNA and MVA vaccines expressing multiple genes (gag, RT, tat, nef and env) from HIV-1 subtype C in chacma baboons (Papio ursinus). The vaccine regimen induced (i) strong T-cell responses, with a median of 4103 spot forming units per 106 peripheral blood mononuclear cells by gamma interferon (IFN-γ) ELISPOT, (ii) broad T-cell responses targeting all five vaccine-expressed genes, with a median of 12 peptides targeted per animal and without any single protein dominating the response, (iii) balanced CD4+ and CD8+ responses, which produced both IFN-γ and interleukin (IL)-2, including IL-2-only responses not detected by the ELISPOT assay, (iv) vaccine memory, which persisted 1 year after immunization and could be boosted further, despite strong anti-vector responses, and (v) mucosal T-cell responses in iliac and mesenteric lymph nodes in two animals tested. The majority of peptide responses mapped contained epitopes previously identified in human HIV infection, and two high-avidity HIV epitope responses were confirmed, indicating the utility of the baboon model for immunogenicity testing. Together, our data show that a combination of DNA and MVA immunization induced robust, durable, multifunctional CD4+ and CD8+ responses in baboons targeting multiple HIV epitopes that may home to mucosal sites. These candidate vaccines, which are immunogenic in this pre-clinical model, represent an alternative to adenoviral-based vaccines and have been approved for clinical trials.

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Ping, Jihui, Tiago J. S. Lopes, Gabriele Neumann, and Yoshihiro Kawaoka. "Development of high-yield influenza B virus vaccine viruses." Proceedings of the National Academy of Sciences 113, no. 51 (December 5, 2016): E8296—E8305. http://dx.doi.org/10.1073/pnas.1616530113.

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The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six “internal” influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.

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Almeida, Renata, Alan Norrish, Mark Levick, David Vetrie, Tom Freeman, Jaak Vilo, Alasdair Ivens, et al. "From genomes to vaccines: Leishmania as a model." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 357, no. 1417 (January 29, 2002): 5–11. http://dx.doi.org/10.1098/rstb.2001.0985.

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The 35 Mb genome of Leishmania should be sequenced by late 2002. It contains approximately 8500 genes that will probably translate into more than 10 000 proteins. In the laboratory we have been piloting strategies to try to harness the power of the genome–proteome for rapid screening of new vaccine candidate. To this end, microarray analysis of 1094 unique genes identified using an EST analysis of 2091 cDNA clones from spliced leader libraries prepared from different developmental stages of Leishmania has been employed. The plan was to identify amastigote–expressed genes that could be used in high–throughput DNA–vaccine screens to identify potential new vaccine candidates. Despite the lack of transcriptional regulation that polycistronic transcription in Leishmania dictates, the data provide evidence for a high level of post–transcriptional regulation of RNA abundance during the developmental cycle of promastigotes in culture and in lesion–derived amastigotes of Leishmania major . This has provided 147 candidates from the 1094 unique genes that are specifically upregulated in amastigotes and are being used in vaccine studies. Using DNA vaccination, it was demonstrated that pooling strategies can work to identify protective vaccines, but it was found that some potentially protective antigens are masked by other disease–exacerbatory antigens in the pool. A total of 100 new vaccine candidates are currently being tested separately and in pools to extend this analysis, and to facilitate retrospective bioinformatic analysis to develop predictive algorithms for sequences that constitute potentially protective antigens. We are also working with other members of the Leishmania Genome Network to determine whether RNA expression determined by microarray analyses parallels expression at the protein level. We believe we are making good progress in developing strategies that will allow rapid translation of the sequence of Leishmania into potential interventions for disease control in humans.

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Guerra, Susana, José Manuel González, Núria Climent, Hugh Reyburn, Luis A. López-Fernández, José L. Nájera, Carmen E. Gómez, et al. "Selective Induction of Host Genes by MVA-B, a Candidate Vaccine against HIV/AIDS." Journal of Virology 84, no. 16 (June 9, 2010): 8141–52. http://dx.doi.org/10.1128/jvi.00749-10.

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ABSTRACT The aim of this study was to define the effects on antigen-presenting cells of the expression of HIV antigens from an attenuated poxvirus vector. We have analyzed the transcriptional changes in gene expression following infection of human immature monocyte-derived dendritic cells (DC) with recombinant modified vaccinia virus Ankara (MVA) expressing the genes encoding the gp120 and Gag-Pol-Nef antigens of HIV type 1 clade B (referred to as MVA-B) versus parental MVA infection. Using microarray technology and real-time reverse transcription-PCR, we demonstrated that the HIV proteins induced the expression of cytokines, cytokine receptors, chemokines, chemokine receptors, and molecules involved in antigen uptake and processing, including major histocompatibility complex (MHC) genes. Levels of mRNAs for interleukin-1, beta interferon, CCR8, and SCYA20 were higher after HIV antigen production. MVA-B infection also modulated the expression of antigen processing and presentation genes: the gene for MICA was upregulated, whereas those for HLA-DRA and HSPA5 were downregulated. Indeed, the increased expression of the gene for MICA, a glycoprotein related to major histocompatibility complex class I molecules, was shown to enhance the interaction between MVA-B-infected target cells and cytotoxic lymphocytes. The expression profiles of the genes for protein kinases such as JAK1 and IRAK2 were activated after HIV antigen expression. Several genes included in the JAK-STAT and mitogen-activated protein kinase signaling pathways were regulated after HIV antigen expression. Our findings provide the first gene signatures in DC of a candidate MVA-B vaccine expressing four HIV antigens and identified the biological roles of some of the regulatory genes, like that for MICA, which will help in the design of more effective MVA-derived vaccines.

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Midthun, K., and A. Z. Kapikian. "Rotavirus vaccines: an overview." Clinical Microbiology Reviews 9, no. 3 (July 1996): 423–34. http://dx.doi.org/10.1128/cmr.9.3.423.

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Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both developed and developing countries. These studies led to the concept that a multivalent vaccine that represented each of the four epidemiologically important VP7 serotypes might be necessary to induce protection in young infants, the target population for vaccination. Human-animal rotavirus reassortants whose gene encoding VP7 was derived from their human rotavirus parent but whose remaining genes were derived from the animal rotavirus parent were developed as vaccine candidates. The greatest experience with a multivalent vaccine to date has been gained with the quadrivalent preparation containing RRV (VP7 serotype 3) and human-RRV reassortants of VP7 serotype 1, 2, and 4 specificity. Preliminary efficacy trial results in the United States have been promising, whereas a study in Peru has shown only limited protection. Human-bovine reassortant vaccines, including a candidate that contains the VP4 gene of a human rotavirus (VP4 serotype 1A), are also being studied.

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Lee, John S., Angela G. Hadjipanayis, and Susan L. Welkos. "Venezuelan Equine Encephalitis Virus-Vectored Vaccines Protect Mice against Anthrax Spore Challenge." Infection and Immunity 71, no. 3 (March 2003): 1491–96. http://dx.doi.org/10.1128/iai.71.3.1491-1496.2003.

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ABSTRACT Anthrax, a disease usually associated with herbivores, is caused by the bacterium Bacillus anthracis. The current vaccine licensed for human use requires a six-dose primary series and yearly boosters and causes reactogenicity in up to 30% of vaccine recipients. A minimally reactogenic vaccine requiring fewer inoculations is warranted. Venezuelan equine encephalitis (VEE) virus has been configured for use as a vaccine vector for a wide variety of immunogens. The VEE vaccine vector is composed of a self-replicating RNA (replicon) containing all of the VEE virus nonstructural genes and a multiple-cloning site in place of the VEE structural genes. Four different anthrax vaccines were constructed by cloning the protective antigen (PA) gene from B. anthracis into the VEE vaccine vector. The anthrax vaccines were produced by assembling the vectors into propagation-deficient VEE replicon particles in vitro. A/J mice inoculated subcutaneously with three doses of the mature 83-kDa PA vaccine were completely protected from challenge with the Sterne strain of B. anthracis. Similar results were obtained with vaccines composed of the PA gene fused to either the B. anthracis secretory sequence or to a tissue plasminogen activator secretory sequence in three additional mouse strains. Mice were unprotected from challenge after inoculation with the carboxy-terminal 63-kDa PA vaccine. These results suggest that these VEE-vectored vaccines may be suitable as candidate vaccines against anthrax.

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Johnson, Philip R., Bruce C. Schnepp, Mary J. Connell, Daniela Rohne, Suzanne Robinson, Georgia R. Krivulka, Carol I. Lord, et al. "Novel Adeno-Associated Virus Vector Vaccine Restricts Replication of Simian Immunodeficiency Virus in Macaques." Journal of Virology 79, no. 2 (January 15, 2005): 955–65. http://dx.doi.org/10.1128/jvi.79.2.955-965.2005.

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ABSTRACT Gene transfer vectors based on recombinant adeno-associated virus (rAAV) are simple, versatile, and safe. While the conventional applications for rAAV vectors have focused on delivery of therapeutic genes, we have developed the system for delivery of vaccine antigens. In particular, we are interested in generating rAAV vectors for use as a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine. To that end, we constructed vaccine vectors that expressed genes from the simian immunodeficiency virus (SIV) for evaluation in the monkey SIV model. After a single intramuscular dose, rAAV/SIV vaccines elicited SIV-specific T cells and antibodies in macaques. Furthermore, immunized animals were able to significantly restrict replication of a live, virulent SIV challenge. These data suggest that rAAV vaccine vectors induced biologically relevant immune responses, and thus, warrant continued development as a viable HIV-1 vaccine candidate.

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Chen, Po-Ling, Alan Yung-Chih Hu, Chun-Yang Lin, Tsai-Chuan Weng, Chia-Chun Lai, Yu-Fen Tseng, Ming-Chu Cheng, et al. "Development of American-Lineage Influenza H5N2 Reassortant Vaccine Viruses for Pandemic Preparedness." Viruses 11, no. 6 (June 11, 2019): 543. http://dx.doi.org/10.3390/v11060543.

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Novel low-pathogenic avian influenza (LPAI) H5N2 viruses hit poultry farms in Taiwan in 2003, and evolved into highly pathogenic avian influenza (HPAI) viruses in 2010. These viruses are reassortant viruses containing HA and NA genes from American-lineage H5N2 and six internal genes from local H6N1 viruses. According to a serological survey, the Taiwan H5N2 viruses can cause asymptomatic infections in poultry workers. Therefore, a development of influenza H5N2 vaccines is desirable for pandemic preparation. In this study, we employed reverse genetics to generate a vaccine virus having HA and NA genes from A/Chicken/CY/A2628/2012 (E7, LPAI) and six internal genes from a Vero cell-adapted high-growth H5N1 vaccine virus (Vero-15). The reassortant H5N2 vaccine virus, E7-V15, presented high-growth efficiency in Vero cells (512 HAU, 107.6 TCID50/mL), and passed all tests for qualification of candidate vaccine viruses. In ferret immunization, two doses of inactivated whole virus antigens (3 μg of HA protein) adjuvanted with alum could induce robust antibody response (HI titre 113.14). In conclusion, we have established reverse genetics to generate a qualified reassortant H5N2 vaccine virus for further development.

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Rostad, Christina A., Christopher C. Stobart, Brian E. Gilbert, Ray J. Pickles, Anne L. Hotard, Jia Meng, Jorge C. G. Blanco, et al. "A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats." Journal of Virology 90, no. 16 (June 8, 2016): 7508–18. http://dx.doi.org/10.1128/jvi.00012-16.

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ABSTRACTAlthough respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log10total PFU and 2.7 log10PFU/g of tissue, respectively, compared to those in unvaccinated animals (P< 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity.IMPORTANCERSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats.

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Kumar, Pawan, Tamer A. Sharafeldin, Rahul Kumar, Qinfeng Huang, Yuying Liang, Sagar M. Goyal, Robert E. Porter, Hinh Ly, and Sunil K. Mor. "Development of a Recombinant Pichinde Virus-Vectored Vaccine against Turkey Arthritis Reovirus and Its Immunological Response Characterization in Vaccinated Animals." Pathogens 10, no. 2 (February 13, 2021): 197. http://dx.doi.org/10.3390/pathogens10020197.

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Vaccination may be an effective way to reduce turkey arthritis reovirus (TARV)-induced lameness in turkey flocks. However, there are currently no commercial vaccines available against TARV infection. Here, we describe the use of reverse genetics technology to generate a recombinant Pichinde virus (PICV) that expresses the Sigma C and/or Sigma B proteins of TARV as antigens. Nine recombinant PICV-based TARV vaccines were developed carrying the wild-type S1 (Sigma C) and/or S3 (Sigma B) genes from three different TARV strains. In addition, three recombinant PICV-based TARV vaccines were produced carrying codon-optimized S1 and/or S3 genes of a TARV strain. The S1 and S3 genes and antigens were found to be expressed in virus-infected cells via reverse transcriptase polymerase chain reaction (RT-PCR) and the direct fluorescent antibody (DFA) technique, respectively. Turkey poults inoculated with the recombinant PICV-based TARV vaccine expressing the bivalent TARV S1 and S3 antigens developed high anti-TARV antibody titers, indicating the immunogenicity (and safety) of this vaccine. Future in vivo challenge studies using a turkey reovirus infection model will determine the optimum dose and protective efficacy of this recombinant virus-vectored candidate vaccine.

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Abd El Ghany, Moataz, Angela Jansen, Simon Clare, Lindsay Hall, Derek Pickard, Robert A. Kingsley, and Gordon Dougan. "Candidate Live, Attenuated Salmonella enterica Serotype Typhimurium Vaccines with Reduced Fecal Shedding Are Immunogenic and Effective Oral Vaccines." Infection and Immunity 75, no. 4 (February 12, 2007): 1835–42. http://dx.doi.org/10.1128/iai.01655-06.

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ABSTRACT Environmental shedding of genetically manipulated microorganisms is an issue impeding the development of new live vaccines. We have investigated the immunogenicity of a number of novel Salmonella enterica serotype Typhimurium oral vaccine candidates that express the fragment C (TetC) component of tetanus toxin and harbor combinations of additional mutations in genes shdA, misL, and ratB that contribute to the persistence of serotype Typhimurium's colonization of the intestine. Serotype Typhimurium aroA (TetC) derivatives harboring additional mutations in either shdA or misL or combinations of these mutations exhibited a marked decrease in shedding of the vaccine strain in the feces of orally vaccinated mice. However, equivalent levels of anti-TetC and anti-Salmonella lipopolysaccharide immunoglobulin G (IgG), IgG1, IgG2a, and IgA were detected in sera of the vaccinated but not of the control mice. Cellular immune responses to TetC were detected in all vaccinated mice, regardless of the presence of the additional mutations in shdA or misL. Further, immunization with serotype Typhimurium aroA candidate vaccines harboring shdA and misL afforded complete protection against challenge with a virulent strain of serotype Typhimurium.

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Blanco, Federico Carlos, Marcelo Soria, María José Gravisaco, María Verónica Bianco, Virginia Meikle, Sergio Garbaccio, Lucas Vagnoni, Angel Adrián Cataldi, and Fabiana Bigi. "Assessment of the Immune Responses Induced in Cattle after Inoculation of aMycobacterium bovisStrain Deleted in Twomce2Genes." Journal of Biomedicine and Biotechnology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/258353.

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The generation of efficient candidate vaccines against bovine tuberculosis will contribute to the control of this zoonotic disease. Rationally attenuatedMycobacterium bovisstrains generated by knockout of virulence genes are promising candidate vaccines. However, to be effective, these candidate vaccines should at least maintain the immunological properties of their virulent parentalM. bovisstrains. Therefore, the aim of this study was to obtain anM. bovisstrain deleted in themce2genes and evaluate the effect of the mutation on the immunological profile elicited by the bacteria in cattle. We showed that the activation of CD4+ T cells in cattle inoculated with the mutant strain was equivalent to that in animals inoculated with the parental strain. Moreover, after in vitro stimulation, peripheral blood mononuclear cells from animals inoculated with the mutant produced higher levels of mRNA Th-1 cytokines than the parental strain. Therefore, these results indicate that themce2mutant is a promising candidate vaccine against bovine tuberculosis.

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Hala, Sharif, Paolo Ribeca, Haya A. Aljami, Suliman A. Alsagaby, Ibrahim Qasim, Sarah C. Gilbert, and Naif Khalaf Alharbi. "Transcriptomic Profiling of Dromedary Camels Immunised with a MERS Vaccine Candidate." Veterinary Sciences 8, no. 8 (August 3, 2021): 156. http://dx.doi.org/10.3390/vetsci8080156.

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Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from whole blood of three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cell, B cell, and NF-κB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

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García-Angulo, Víctor A., Anjana Kalita, Mridul Kalita, Luis Lozano, and Alfredo G. Torres. "Comparative Genomics and Immunoinformatics Approach for the Identification of Vaccine Candidates for Enterohemorrhagic Escherichia coli O157:H7." Infection and Immunity 82, no. 5 (March 4, 2014): 2016–26. http://dx.doi.org/10.1128/iai.01437-13.

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ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) O157:H7 strains are major human food-borne pathogens, responsible for bloody diarrhea and hemolytic-uremic syndrome worldwide. Thus far, there is no vaccine for humans against EHEC infections. In this study, a comparative genomics analysis was performed to identify EHEC-specific antigens useful as potential vaccines. The genes present in both EHEC EDL933 and Sakai strains but absent in nonpathogenicE. coliK-12 and HS strains were subjected to anin silicoanalysis to identify secreted or surface-expressed proteins. We obtained a total of 65 gene-encoding protein candidates, which were subjected to immunoinformatics analysis. Our criteria of selection aided in categorizing the candidates as high, medium, and low priority. Three members of each group were randomly selected and cloned into pVAX-1.Candidates were pooled accordingly to their priority group and tested for immunogenicity against EHEC O157:H7 using a murine model of gastrointestinal infection. The high-priority (HP) pool, containing genes encoding a Lom-like protein (pVAX-31), a putative pilin subunit (pVAX-12), and a fragment of the type III secretion structural protein EscC (pVAX-56.2), was able to induce the production of EHEC IgG and sIgA in sera and feces. HP candidate-immunized mice displayed elevated levels of Th2 cytokines and diminished cecum colonization after wild-type challenge. Individually tested HP vaccine candidates showed that pVAX-12 and pVAX-56.2 significantly induced Th2 cytokines and production of fecal EHEC sIgA, with pVAX-56.2 reducing EHEC cecum colonization. We describe here a bioinformatics approach able to identify novel vaccine candidates potentially useful for preventing EHEC O157:H7 infections.

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Rajashekara, Gireesh, David A. Glover, Menachem Banai, David O'Callaghan, and Gary A. Splitter. "Attenuated Bioluminescent Brucella melitensis Mutants GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091) Confer Protection in Mice." Infection and Immunity 74, no. 5 (May 2006): 2925–36. http://dx.doi.org/10.1128/iai.74.5.2925-2936.2006.

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ABSTRACT In vivo bioluminescence imaging is a persuasive approach to investigate a number of issues in microbial pathogenesis. Previously, we have applied bioluminescence imaging to gain greater insight into Brucella melitensis pathogenesis. Endowing Brucella with bioluminescence allowed direct visualization of bacterial dissemination, pattern of tissue localization, and the contribution of Brucella genes to virulence. In this report, we describe the pathogenicity of three attenuated bioluminescent B. melitensis mutants, GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091), and the dynamics of bioluminescent virulent bacterial infection following vaccination with these mutants. The virB4, galE, and BMEI1090-BMEI1091 mutants were attenuated in interferon regulatory factor 1-deficient (IRF-1−/−) mice; however, only the GR019 (virB4) mutant was attenuated in cultured macrophages. Therefore, in vivo imaging provides a comprehensive approach to identify virulence genes that are relevant to in vivo pathogenesis. Our results provide greater insights into the role of galE in virulence and also suggest that BMEI1090 and downstream genes constitute a novel set of genes involved in Brucella virulence. Survival of the vaccine strain in the host for a critical period is important for effective Brucella vaccines. The galE mutant induced no changes in liver and spleen but localized chronically in the tail and protected IRF-1−/− and wild-type mice from virulent challenge, implying that this mutant may serve as a potential vaccine candidate in future studies and that the direct visualization of Brucella may provide insight into selection of improved vaccine candidates.

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Pérez, Patricia, María Q. Marín, Adrián Lázaro-Frías, Carlos Óscar S. Sorzano, Carmen E. Gómez, Mariano Esteban, and Juan García-Arriaza. "Deletion of Vaccinia Virus A40R Gene Improves the Immunogenicity of the HIV-1 Vaccine Candidate MVA-B." Vaccines 8, no. 1 (February 6, 2020): 70. http://dx.doi.org/10.3390/vaccines8010070.

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Development of a safe and efficacious vaccine against the HIV/AIDS pandemic remains a major scientific goal. We previously described an HIV/AIDS vaccine based on the modified vaccinia virus Ankara (MVA) expressing HIV-1 gp120 and Gag-Pol-Nef (GPN) of clade B (termed MVA-B), which showed moderate immunogenicity in phase I prophylactic and therapeutic clinical trials. Here, to improve the immunogenicity of MVA-B, we generated a novel recombinant virus, MVA-B ΔA40R, by deleting in the MVA-B genome the vaccinia virus (VACV) A40R gene, which encodes a protein with unknown immune function. The innate immune responses triggered by MVA-B ΔA40R in infected human macrophages, in comparison to parental MVA-B, revealed an increase in the mRNA expression levels of interferon (IFN)-β, IFN-induced genes, and chemokines. Compared to priming with DNA-B (a mixture of DNA-gp120 plus DNA-GPN) and boosting with MVA-B, mice immunized with a DNA-B/MVA-B ΔA40R regimen induced higher magnitude of adaptive and memory HIV-1-specific CD4+ and CD8+ T-cell immune responses that were highly polyfunctional, mainly directed against Env. and of an effector memory phenotype, together with enhanced levels of antibodies against HIV-1 gp120. Reintroduction of the A40R gene into the MVA-B ΔA40R genome (virus termed MVA-B ΔA40R-rev) promoted in infected cells high mRNA and protein A40 levels, with A40 protein localized in the cell membrane. MVA-B ΔA40R-rev significantly reduced mRNA levels of IFN-β and of several other innate immune-related genes in infected human macrophages. In immunized mice, MVA-B ΔA40R-rev reduced the magnitude of the HIV-1-specific CD4+ and CD8+ T cell responses compared to MVA-B ΔA40R. These results revealed an immunosuppressive role of the A40 protein, findings relevant for the optimization of poxvirus vectors as vaccines.

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Hu, Pingsheng, Xiaoming Chen, Lihong Huang, Shukai Liu, Fuyu Zang, Jinchao Xing, Youyue Zhang, et al. "A highly pathogenic porcine reproductive and respiratory syndrome virus candidate vaccine based on Japanese encephalitis virus replicon system." PeerJ 5 (July 20, 2017): e3514. http://dx.doi.org/10.7717/peerj.3514.

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In the swine industry, porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease which causes heavy economic losses worldwide. Effective prevention and disease control is an important issue. In this study, we described the construction of a Japanese encephalitis virus (JEV) DNA-based replicon with a cytomegalovirus (CMV) promoter based on the genome of Japanese encephalitis live vaccine virus SA14-14-2, which is capable of offering a potentially novel way to develop and produce vaccines against a major pathogen of global health. This JEV DNA-based replicon contains a large deletion in the structural genes (C-prM-E). A PRRSV GP5/M was inserted into the deletion position of JEV DNA-based replicons to develop a chimeric replicon vaccine candidate for PRRSV. The results showed that BALB/c mice models with the replicon vaccines pJEV-REP-G-2A-M-IRES and pJEV-REP-G-2A-M stimulated antibody responses and induced a cellular immune response. Analysis of ELSA data showed that vaccination with the replicon vaccine expressing GP5/M induced a better antibodies response than traditional DNA vaccines. Therefore, the results suggested that this ectopic expression system based on JEV DNA-based replicons may represent a useful molecular platform for various biological applications, and the JEV DNA-based replicons expressing GP5/M can be further developed into a novel, safe vaccine candidate for PRRS.

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Marín, María Q., Patricia Pérez, Carmen E. Gómez, Carlos Óscar S. Sorzano, Mariano Esteban, and Juan García-Arriaza. "Removal of the C6 Vaccinia Virus Interferon-β Inhibitor in the Hepatitis C Vaccine Candidate MVA-HCV Elicited in Mice High Immunogenicity in Spite of Reduced Host Gene Expression." Viruses 10, no. 8 (August 8, 2018): 414. http://dx.doi.org/10.3390/v10080414.

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Hepatitis C virus (HCV) represents a major global health problem for which a vaccine is not available. Modified vaccinia virus Ankara (MVA)-HCV is a unique HCV vaccine candidate based in the modified vaccinia virus Ankara (MVA) vector expressing the nearly full-length genome of HCV genotype 1a that elicits CD8+ T-cell responses in mice. With the aim to improve the immune response of MVA-HCV and because of the importance of interferon (IFN) in HCV infection, we deleted in MVA-HCV the vaccinia virus (VACV) C6L gene, encoding an inhibitor of IFN-β that prevents activation of the interferon regulatory factors 3 and 7 (IRF3 and IRF7). The resulting vaccine candidate (MVA-HCV ΔC6L) expresses all HCV antigens and deletion of C6L had no effect on viral growth in permissive chicken cells. In human monocyte-derived dendritic cells, infection with MVA-HCV ΔC6L triggered severe down-regulation of IFN-β, IFN-β-induced genes, and cytokines in a manner similar to MVA-HCV, as defined by real-time polymerase chain reaction (PCR) and microarray analysis. In infected mice, both vectors had a similar profile of recruited immune cells and induced comparable levels of adaptive and memory HCV-specific CD8+ T-cells, mainly against p7 + NS2 and NS3 HCV proteins, with a T cell effector memory (TEM) phenotype. Furthermore, antibodies against E2 were also induced. Overall, our findings showed that while these vectors had a profound inhibitory effect on gene expression of the host, they strongly elicited CD8+ T cell and humoral responses against HCV antigens and to the virus vector. These observations add support to the consideration of these vectors as potential vaccine candidates against HCV.

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Zhang, Jingyuan, Yanyan Zhang, Teng Chen, Jinjin Yang, Huixian Yue, Lidong Wang, Xintao Zhou, et al. "Deletion of the L7L-L11L Genes Attenuates ASFV and Induces Protection against Homologous Challenge." Viruses 13, no. 2 (February 8, 2021): 255. http://dx.doi.org/10.3390/v13020255.

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African swine fever (ASF), caused by the African swine fever virus (ASFV), is a major epidemic disease endangering the swine industry. Although a number of vaccine candidates have been reported, none are commercially available yet. To explore the effect of unknown genes on the biological characteristics of ASFV and the possibility of a gene-deleted isolate as a vaccine candidate, the strain SY18ΔL7-11, with deletions of L7L–L11L genes from ASFV SY18, was constructed, and its biological properties were analyzed. The results show that deletion of genes L7L-L11L did not affect replication of the virus in vitro. Virulence of SY18△L7-11 was significantly reduced, as 11 of the 12 pigs survived for 28 days after intramuscular inoculation with a low dose (103 TCID50) or a high dose (106 TCID50) of SY18ΔL7-11. All 11 surviving pigs were completely protected against challenge with the parental ASFV SY18 on 28 days postinoculation (dpi). Transient fever and/or irregularly low levels of genomic DNA in the blood were monitored in some pigs after inoculation. No ASF clinical signs or viremia were monitored after challenge. Antibodies to ASFV were induced in all pigs from 14 to 21 days postinoculation. IFN-γ was detected in most of the inoculated pigs, which is usually inhibited in ASFV-infected pigs. Overall, the results demonstrate that SY18ΔL7-11 is a candidate for further constructing safer vaccine(s), with better joint deletions of other gene(s) related to virulence.

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Yatoo, Mohd, Oveas Parray, Muheet, Riyaz Bhat, Qurat Nazir, Abrar Haq, Hamid Malik, et al. "Novel Candidates for Vaccine Development Against Mycoplasma Capricolum Subspecies Capripneumoniae (Mccp)—Current Knowledge and Future Prospects." Vaccines 7, no. 3 (July 23, 2019): 71. http://dx.doi.org/10.3390/vaccines7030071.

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Exploration of novel candidates for vaccine development against Mycoplasma capricolum subspecies capripneumoniae (Mccp), the causative agent of contagious caprine pleuropneumonia (CCPP), has recently gained immense importance due to both the increased number of outbreaks and the alarming risk of transboundary spread of disease. Treatment by antibiotics as the only therapeutic strategy is not a viable option due to pathogen persistence, economic issues, and concerns of antibiotic resistance. Therefore, prophylactics or vaccines are becoming important under the current scenario. For quite some time inactivated, killed, or attenuated vaccines proved to be beneficial and provided good immunity up to a year. However, their adverse effects and requirement for larger doses led to the need for production of large quantities of Mccp. This is challenging because the required culture medium is costly and Mycoplasma growth is fastidious and slow. Furthermore, quality control is always an issue with such vaccines. Currently, novel candidate antigens including capsular polysaccharides (CPS), proteins, enzymes, and genes are being evaluated for potential use as vaccines. These have shown potential immunogenicity with promising results in eliciting protective immune responses. Being easy to produce, specific, effective and free from side effects, these novel vaccine candidates can revolutionize vaccination against CCPP. Use of novel proteomic approaches, including sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional gel electrophoresis, immunoblotting, matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry, tandem mass spectroscopy, fast protein liquid chromatography (FPLC), bioinformatics, computerized simulation and genomic approaches, including multilocus sequence analysis, next-generation sequencing, basic local alignment search tool (BLAST), gene expression, and recombinant expression, will further enable recognition of ideal antigenic proteins and virulence genes with vaccination potential.

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Haddad, Diana, Erika Bilcikova, Adam A. Witney, Jane M. Carlton, Charles E. White, Peter L. Blair, Rana Chattopadhyay, et al. "Novel Antigen Identification Method for Discovery of Protective Malaria Antigens by Rapid Testing of DNA Vaccines Encoding Exons from the Parasite Genome." Infection and Immunity 72, no. 3 (March 2004): 1594–602. http://dx.doi.org/10.1128/iai.72.3.1594-1602.2004.

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ABSTRACT We describe a novel approach for identifying target antigens for preerythrocytic malaria vaccines. Our strategy is to rapidly test hundreds of DNA vaccines encoding exons from the Plasmodium yoelii yoelii genomic sequence. In this antigen identification method, we measure reduction in parasite burden in the liver after sporozoite challenge in mice. Orthologs of protective P. y. yoelii genes can then be identified in the genomic databases of Plasmodium falciparum and Plasmodium vivax and investigated as candidate antigens for a human vaccine. A pilot study to develop the antigen identification method approach used 192 P. y. yoelii exons from genes expressed during the sporozoite stage of the life cycle. A total of 182 (94%) exons were successfully cloned into a DNA immunization vector with the Gateway cloning technology. To assess immunization strategies, mice were vaccinated with 19 of the new DNA plasmids in addition to the well-characterized protective plasmid encoding P. y. yoelii circumsporozoite protein. Single plasmid immunization by gene gun identified a novel vaccine target antigen which decreased liver parasite burden by 95% and which has orthologs in P. vivax and P. knowlesi but not P. falciparum. Intramuscular injection of DNA plasmids produced a different pattern of protective responses from those seen with gene gun immunization. Intramuscular immunization with plasmid pools could reduce liver parasite burden in mice despite the fact that none of the plasmids was protective when given individually. We conclude that high-throughput cloning of exons into DNA vaccines and their screening is feasible and can rapidly identify new malaria vaccine candidate antigens.

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Luo, Deyan, Bing Ni, Peng Li, Wei Shi, Songle Zhang, Yue Han, Liwei Mao, Yangdong He, Yuzhang Wu, and Xiliang Wang. "Protective Immunity Elicited by a Divalent DNA Vaccine Encoding Both the L7/L12 and Omp16 Genes of Brucella abortus in BALB/c Mice." Infection and Immunity 74, no. 5 (May 2006): 2734–41. http://dx.doi.org/10.1128/iai.74.5.2734-2741.2006.

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ABSTRACT This study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this divalent DNA vaccine into BALB/c mice elicited markedly both humoral and cellular immune responses. The specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. In addition, the dual-gene DNA vaccine elicited a strong T-cell proliferative response and induced a large amount of gamma interferon-producing T cells upon restimulation in vitro with recombinant fusion protein L7/L12-Omp16, suggesting the induction of a typical T-helper-1-dominated immune response in vivo. This divalent DNA vaccine could also induce a significant level of protection against challenge with the virulent strain B. abortus 544 in BALB/c mice. Furthermore, the protection level induced by the divalent DNA vaccine was significantly higher than that induced by the univalent DNA vaccines pcDNA3.1-L7/L12 or pcDNA3.1-Omp16. Taken together, the results of this study verify for the first time that the Omp16 gene can be a candidate target for a DNA vaccine against brucellosis. Additionally, a divalent genetic vaccine based on the L7/L12 and Omp16 genes can elicit a stronger cellular immune response and better immunoprotection than the relevant univalent vaccines can.

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Kawaguchiya, Urushibara, Aung, Shinagawa, Takahashi, and Kobayashi. "Prevalence of Various Vaccine Candidate Proteins in Clinical Isolates of Streptococcus pneumoniae: Characterization of the Novel Pht Fusion Proteins PhtA/B and PhtA/D." Pathogens 8, no. 4 (September 24, 2019): 162. http://dx.doi.org/10.3390/pathogens8040162.

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Pneumococcal proteins unrelated to serotypes are considered to be candidates of antigens in next-generation vaccines. In the present study, the prevalence of vaccine candidate protein genes, along with serotypes and antimicrobial resistance determinants, was investigated in a total of 57 isolates obtained from a tertiary care hospital in Japan. All of the pediatric isolates and 76.6% of the adult isolates did not belong to PCV13 (a 13-valent pneumococcal conjugate vaccine) serotypes, and 70.2% of all isolates showed multidrug resistance. All of the isolates had ply, pavA, nanA, and nanB, and high prevalence was noted for the pspA and pspC genes (96.5% and 78.9%, respectively). Detection rates for the pneumococcal histidine triad protein (Pht) genes phtA, phtB, phtD, and phtE were 49.1%, 26.3%, 61.4%, and 100%, respectively. Two fusion-type genes, phtA/B and phtA/D, were identified, with a prevalence of 36.9% and 14.0%, respectively. These fusion types showed 78.1–90.0% nucleotide sequence identity with phtA, phtB, and phtD. The most prevalent pht profile was phtA + phtD + phtE (26.3%), followed by phtA/B + phtE (19.3%) and phtA/B + phtD + phtE (17.5%), while pht profiles including phtD and/or phtA/phtD were found in 71.9% of isolates. The present study revealed the presence of two fusion types of Pht and their unexpectedly high prevalence. These fusion types, as well as PhtA and PhtB, contained sequences similar to the B cell epitopes that have been previously reported for PhtD.

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Dearlove, Bethany, Eric Lewitus, Hongjun Bai, Yifan Li, Daniel B. Reeves, M. Gordon Joyce, Paul T. Scott, et al. "A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants." Proceedings of the National Academy of Sciences 117, no. 38 (August 31, 2020): 23652–62. http://dx.doi.org/10.1073/pnas.2008281117.

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The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based. Using 18,514 sequences, we perform phylogenetic, population genetics, and structural bioinformatics analyses. We find limited diversity across SARS-CoV-2 genomes: Only 11 sites show polymorphisms in >5% of sequences; yet two mutations, including the D614G mutation in Spike, have already become consensus. Because SARS-CoV-2 is being transmitted more rapidly than it evolves, the viral population is becoming more homogeneous, with a median of seven nucleotide substitutions between genomes. There is evidence of purifying selection but little evidence of diversifying selection, with substitution rates comparable across structural versus nonstructural genes. Finally, the Wuhan-Hu-1 reference sequence for the Spike protein, which is the basis for different vaccine candidates, matches optimized vaccine inserts, being identical to an ancestral sequence and one mutation away from the consensus. While the rapid spread of the D614G mutation warrants further study, our results indicate that drift and bottleneck events can explain the minimal diversity found among SARS-CoV-2 sequences. These findings suggest that a single vaccine candidate should be efficacious against currently circulating lineages.

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Hoshino, Yo, Sarat K. Dalai, Kening Wang, Lesley Pesnicak, Tsz Y. Lau, David M. Knipe, Jeffrey I. Cohen, and Stephen E. Straus. "Comparative Efficacy and Immunogenicity of Replication-Defective, Recombinant Glycoprotein, and DNA Vaccines for Herpes Simplex Virus 2 Infections in Mice and Guinea Pigs." Journal of Virology 79, no. 1 (January 1, 2005): 410–18. http://dx.doi.org/10.1128/jvi.79.1.410-418.2005.

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ABSTRACT Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8+-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.

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Tzelos, T., J. B. Matthews, B. Whitelaw, and D. P. Knox. "Marker genes for activation of the RNA interference (RNAi) pathway in the free-living nematode Caenorhabditis elegans and RNAi development in the ovine nematode Teladorsagia circumcincta." Journal of Helminthology 89, no. 2 (December 18, 2013): 208–16. http://dx.doi.org/10.1017/s0022149x13000801.

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AbstractThe nematode Teladorsagiacircumcincta is a major cause of parasitic gastroenteritis in sheep in temperate regions. The development of resistance to the major anthelmintic classes used for its control is a threat to small ruminant farming sustainability. Vaccination is a potential alternative control method for this nematode. Gene datasets can be exploited to identify potential vaccine candidates and these validated further by methods such as RNA interference (RNAi) prior to vaccine trials. Previous reports indicate that RNAi in parasitic nematodes is inconsistent and, to date, there are no internal controls that indicate activation of the RNAi pathway in response to double-stranded RNA (dsRNA). The present aims were to determine whether or not the transcription levels of potential marker genes in the RNAi pathway could indicate activation of the pathway in Caenorhabditis elegans and to develop an RNAi platform in T. circumcincta. In C. elegans, transcript levels of three candidate marker genes, Ce-dcr-1 (Dicer), Ce-ego-1 (Enhancer of Glp-One family member) and Ce-rsd-3 (RNAi Spreading Defective), were analysed and results indicated that activation of the pathway had no effect on transcript levels of these genes. In T. circumcincta, two vaccine candidate genes from the Activation-associated Secreted Protein (ASP) family were targets for knockdown. RNAi experiments showed successful silencing of both targets, although inconsistencies in efficacy were observed. After testing a number of parameters that might affect variability, it was found that the length of the storage period of the larvae plays an important role in the consistency of the RNAi results.

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March, John B., Catherine D. Jepson, Jason R. Clark, Makrina Totsika, and Michael J. Calcutt. "Phage Library Screening for the Rapid Identification and In Vivo Testing of Candidate Genes for a DNA Vaccine against Mycoplasma mycoides subsp. mycoides Small Colony Biotype." Infection and Immunity 74, no. 1 (January 2006): 167–74. http://dx.doi.org/10.1128/iai.74.1.167-174.2006.

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ABSTRACT A new strategy for rapidly selecting and testing genetic vaccines has been developed, in which a whole genome library is cloned into a bacteriophage λ ZAP Express vector which contains both prokaryotic (Plac) and eukaryotic (PCMV) promoters upstream of the insertion site. The phage library is plated on Escherichia coli cells, immunoblotted, and probed with hyperimmune and/or convalescent-phase antiserum to rapidly identify vaccine candidates. These are then plaque purified and grown as liquid lysates, and whole bacteriophage particles are then used directly to immunize the host, following which PCMV-driven expression of the candidate vaccine gene occurs. In the example given here, a semirandom genome library of the bovine pathogen Mycoplasma mycoides subsp. mycoides small colony (SC) biotype was cloned into λ ZAP Express, and two strongly immunodominant clones, λ-A8 and λ-B1, were identified and subsequently tested for vaccine potential against M. mycoides subsp. mycoides SC biotype-induced mycoplasmemia. Sequencing and immunoblotting indicated that clone λ-A8 expressed an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible M. mycoides subsp. mycoides SC biotype protein with a 28-kDa apparent molecular mass, identified as a previously uncharacterized putative lipoprotein (MSC_0397). Clone λ-B1 contained several full-length genes from the M. mycoides subsp. mycoides SC biotype pyruvate dehydrogenase region, and two IPTG-independent polypeptides, of 29 kDa and 57 kDa, were identified on immunoblots. Following vaccination, significant anti-M. mycoides subsp. mycoides SC biotype responses were observed in mice vaccinated with clones λ-A8 and λ-B1. A significant stimulation index was observed following incubation of splenocytes from mice vaccinated with clone λ-A8 with whole live M. mycoides subsp. mycoides SC biotype cells, indicating cellular proliferation. After challenge, mice vaccinated with clone λ-A8 also exhibited a reduced level of mycoplasmemia compared to controls, suggesting that the MSC_0397 lipoprotein has a protective effect in the mouse model when delivered as a bacteriophage DNA vaccine. Bacteriophage-mediated immunoscreening using an appropriate vector system offers a rapid and simple technique for the identification and immediate testing of putative candidate vaccines from a variety of pathogens.

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Jacobsson, Susanne, Sara Thulin, Paula Mölling, Magnus Unemo, Maurizio Comanducci, Rino Rappuoli, and Per Olcén. "Sequence constancies and variations in genes encoding three new meningococcal vaccine candidate antigens." Vaccine 24, no. 12 (March 2006): 2161–68. http://dx.doi.org/10.1016/j.vaccine.2005.11.006.

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Lal, Altaf A. "Molecular and immunologic aspects of diversity in P. falciparum Candidate Vaccine antigen genes." Parasitology International 47 (August 1998): 58. http://dx.doi.org/10.1016/s1383-5769(98)80105-0.

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Kumar, Hirdesh, Friedrich Frischknecht, Gunnar R. Mair, and James Gomes. "In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage." Infection, Genetics and Evolution 36 (December 2015): 72–81. http://dx.doi.org/10.1016/j.meegid.2015.09.002.

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Amonov, Malik, Nordin Simbak, Wan Mohd Razin Wan Hassan, Salwani Ismail, Nor Iza A. Rahman, Stuart C. Clarke, and Chew Chieng Yeo. "Disruption of the cpsE and endA Genes Attenuates Streptococcus pneumoniae Virulence: Towards the Development of a Live Attenuated Vaccine Candidate." Vaccines 8, no. 2 (April 15, 2020): 187. http://dx.doi.org/10.3390/vaccines8020187.

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The majority of deaths due to Streptococcus pneumoniae infections are in developing countries. Although polysaccharide-based pneumococcal vaccines are available, newer types of vaccines are needed to increase vaccine affordability, particularly in developing countries, and to provide broader protection across all pneumococcal serotypes. To attenuate pneumococcal virulence with the aim of engineering candidate live attenuated vaccines (LAVs), we constructed knockouts in S. pneumoniae D39 of one of the capsular biosynthetic genes, cpsE that encodes glycosyltransferase, and the endonuclease gene, endA, that had been implicated in the uptake of DNA from the environment as well as bacterial escape from neutrophil-mediated killing. The cpsE gene knockout significantly lowered peak bacterial density, BALB/c mice nasopharyngeal (NP) colonisation but increased biofilm formation when compared to the wild-type D39 strain as well as the endA gene knockout mutant. All constructed mutant strains were able to induce significantly high serum and mucosal antibody response in BALB/c mice. However, the cpsE-endA double mutant strain, designated SPEC, was able to protect mice from high dose mucosal challenge of the D39 wild-type. Furthermore, SPEC showed 23-fold attenuation of virulence compared to the wild-type. Thus, the cpsE-endA double-mutant strain could be a promising candidate for further development of a LAV for S. pneumoniae.

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Pappas, Claudia, Yumiko Matsuoka, David E. Swayne, and Ruben O. Donis. "Development and Evaluation of an Influenza Virus Subtype H7N2 Vaccine Candidate for Pandemic Preparedness." Clinical and Vaccine Immunology 14, no. 11 (October 3, 2007): 1425–32. http://dx.doi.org/10.1128/cvi.00174-07.

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ABSTRACT Influenza virus of the H7N2 subtype has been introduced into noncommercial poultry in the United States, and this probably resulted in incidents of transmission of H7N2 virus to humans, documented in 2002 and 2003. This virus could be considered a potential threat to public health if it acquired person-to-person transmissibility. A favored approach for global pandemic preparedness includes development of prepandemic vaccines for any potential pandemic virus. To this end, we created a high-growth reassortant virus (H7N2-PR8) containing the genes for the hemagglutinin and the neuraminidase from a low-pathogenicity (H7N2) virus strain and the remaining six genes from a human vaccine strain (H1N1). The reassortant strain was evaluated to assess its antigenicity, safety, and protective efficacy using a mouse model. Antigenicity studies using ferret antibodies raised against H7N2-PR8 indicated that this virus confers broad cross-reactivity with divergent H7 viruses of different years and lineages. Mice and chickens inoculated with high doses of H7N2-PR8 supported virus replication but survived, indicating that this virus is comparable to other avian viruses of low pathogenicity. To assess the protective efficacy of H7N2-PR8, mice were immunized with two doses of formalin-inactivated H7N2-PR8, alone or with alum. Vaccinated mice subsequently challenged with highly pathogenic viruses from homologous and heterologous lineages A/Canada/444/04 (H7N3) and A/Netherlands/219/03 (H7N7) showed pronounced reduction of wild-type virus replication. These studies indicate that H7N2-PR8 is immunogenic, safe, and protective in animal models; these are the essential attributes to qualify for phase I human clinical trials as a prepandemic vaccine.

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Mezhenskaya, Daria, Irina Isakova-Sivak, Victoria Matyushenko, Svetlana Donina, Andrey Rekstin, Konstantin Sivak, Kirill Yakovlev, et al. "Universal Live-Attenuated Influenza Vaccine Candidates Expressing Multiple M2e Epitopes Protect Ferrets against a High-Dose Heterologous Virus Challenge." Viruses 13, no. 7 (June 30, 2021): 1280. http://dx.doi.org/10.3390/v13071280.

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The development of an influenza vaccine with broad protection and durability remains an attractive idea due to the high mutation rate of the influenza virus. An extracellular domain of Matrix 2 protein (M2e) is among the most attractive target for the universal influenza vaccine owing to its high conservancy rate. Here, we generated two recombinant live attenuated influenza vaccine (LAIV) candidates encoding four M2e epitopes representing consensus sequences of human, avian and swine influenza viruses, and studied them in a preclinical ferret model. Both LAIV+4M2e viruses induced higher levels of M2e-specific antibodies compared to the control LAIV strain, with the LAIV/HA+4M2e candidate being significantly more immunogenic than the LAIV/NS+4M2e counterpart. A high-dose heterosubtypic influenza virus challenge revealed the highest degree of protection after immunization with LAIV/HA+4M2e strain, followed by the NS-modified LAIV and the classical LAIV virus. Furthermore, only the immune sera from the LAIV/HA+4M2e-immunized ferrets protected mice from a panel of lethal influenza viruses encoding M genes of various origins. These data suggest that the improved cross-protection of the LAIV/HA+4M2e universal influenza vaccine candidate was mediated by the M2e-targeted antibodies. Taking into account the safety profile and improved cross-protective potential, the LAIV/HA+4M2e vaccine warrants its further evaluation in a phase I clinical trial.

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Jackson, Mary, Susan W. Phalen, Micheline Lagranderie, Danielle Ensergueix, Pierre Chavarot, Gilles Marchal, David N. McMurray, Brigitte Gicquel, and Christophe Guilhot. "Persistence and Protective Efficacy of aMycobacterium tuberculosis Auxotroph Vaccine." Infection and Immunity 67, no. 6 (June 1, 1999): 2867–73. http://dx.doi.org/10.1128/iai.67.6.2867-2873.1999.

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ABSTRACT New vaccines against tuberculosis are urgently required because of the impressive incidence of this disease worldwide and the highly variable protective efficacy of the current vaccine. The possibility of creating new live vaccines by the rational attenuation of strains from the Mycobacterium tuberculosis complex was investigated. Two auxotrophic mutants of M. tuberculosis and M. bovis BCG were constructed by disruption of one of their purine biosynthetic genes. These mutants appeared unable to multiply in vitro within mouse bone-marrow derived macrophages. They were also attenuated in vivo in the mouse and guinea pig animal models. In guinea pigs, the two mutants induced strong delayed-type hypersensitivity response to purified protein derivative. In a preliminary experiment, the two mutants were compared to the BCG vaccine for their protective efficacy in a challenge against aerosolized virulent M. tuberculosisin the guinea pig model. Both mutants conferred some level of protection. These experiments demonstrate that the rational attenuation of M. tuberculosis could lead to the design of new candidate live vaccines against tuberculosis.

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Stokes, Neil R., Xin Zhou, Stephen J. Meltzer, and James B. Kaper. "Transcriptional Responses of Intestinal Epithelial Cells to Infection with Vibrio cholerae." Infection and Immunity 72, no. 7 (July 2004): 4240–48. http://dx.doi.org/10.1128/iai.72.7.4240-4248.2004.

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ABSTRACT Vibrio cholerae is a noninvasive enteric bacterium that causes the severe diarrheal disease cholera. Candidate cholera vaccines have been engineered by deleting genes encoding known virulence factors in V. cholerae; however, many of these attenuated strains were still reactogenic in human volunteers. In this study, DNA arrays were utilized to monitor the transcriptional responses of human intestinal epithelial cells (T84) to eight strains of V. cholerae, including attenuated, toxigenic, and environmental isolates. cDNA probes generated from host RNA samples were hybridized against low- and high-density gene arrays. V. cholerae induced the transcription of a variety of host genes and repressed the expression of a lower number of genes. Expression patterns were confirmed for certain genes by reverse transcriptase PCR and enzyme-linked immunosorbent assays. A core subset of genes was found to be differentially regulated in all experiments. These genes included genes involved in innate mucosal immunity, intracellular signaling, and cellular proliferation. Reactogenic vaccine strains induced greater expression of genes for certain proinflammatory cytokines than nonreactogenic strains. Wild-type and attenuated derivatives induced and repressed many genes in common, although there were differences in the transcription profiles. These results indicate that the types of host genes modulated by attenuated V. cholerae, and the extent of their induction, may mediate the symptoms seen with reactogenic cholera vaccine strains.

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Bazhan, Sergei I., Denis V. Antonets, Larisa I. Karpenko, Svetlana F. Oreshkova, Olga N. Kaplina, Ekaterina V. Starostina, Sergei G. Dudko, Sofia A. Fedotova, and Alexander A. Ilyichev. "In silico Designed Ebola Virus T-Cell Multi-Epitope DNA Vaccine Constructions Are Immunogenic in Mice." Vaccines 7, no. 2 (March 29, 2019): 34. http://dx.doi.org/10.3390/vaccines7020034.

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Background: The lack of effective vaccines against Ebola virus initiates a search for new approaches to overcoming this problem. The aim of the study was to design artificial polyepitope T-cell immunogens––candidate DNA vaccines against Ebola virus and to evaluate their capacity to induce a specific immune response in a laboratory animal model. Method: Design of two artificial polyepitope T-cell immunogens, one of which (EV.CTL) includes cytotoxic and the other (EV.Th)––T-helper epitopes of Ebola virus proteins was carried out using original TEpredict/PolyCTLDesigner software. Synthesized genes were cloned in pcDNA3.1 plasmid vector. Target gene expression was estimated by synthesis of specific mRNAs and proteins in cells transfected with recombinant plasmids. Immunogenicity of obtained DNA vaccine constructs was evaluated according to their capacity to induce T-cell response in BALB/c mice using IFNγ ELISpot and ICS. Results: We show that recombinant plasmids pEV.CTL and pEV.Th encoding artificial antigens provide synthesis of corresponding mRNAs and proteins in transfected cells, as well as induce specific responses both to CD4+ and CD8+ T-lymphocytes in immunized animals. Conclusions: The obtained recombinant plasmids can be regarded as promising DNA vaccine candidates in future studies of their capacity to induce cytotoxic and protective responses against Ebola virus.

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Ehrenberg, Philip K., Shida Shangguan, Biju Issac, Galit Alter, Aviva Geretz, Taisuke Izumi, Christopher Bryant, et al. "A vaccine-induced gene expression signature correlates with protection against SIV and HIV in multiple trials." Science Translational Medicine 11, no. 507 (August 28, 2019): eaaw4236. http://dx.doi.org/10.1126/scitranslmed.aaw4236.

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Current HIV vaccines are only partially efficacious, presenting an opportunity to identify correlates of protection and, thereby, potential insight into mechanisms that prevent HIV acquisition. Two independent preclinical challenge studies in nonhuman primates (NHPs) previously showed partial efficacy of a mosaic adenovirus 26 (Ad26)–based HIV-1 vaccine candidate. To investigate the basis of this protection, we performed whole transcriptomics profiling by RNA sequencing (RNA-seq) in sorted lymphocytes from peripheral blood samples taken during these studies at different time points after vaccination but before challenge. We observed a transcriptional signature in B cells that associated with protection from acquisition of simian immunodeficiency virus (SIV) or the simian-human immunodeficiency virus (SHIV) in both studies. Strong antibody responses were elicited, and genes from the signature for which expression was enriched specifically associated with higher magnitude of functional antibody responses. The same gene expression signature also associated with protection in RV144 in the only human HIV vaccine trial to date that has shown efficacy and in two additional NHP studies that evaluated similar canarypox-based vaccine regimens. A composite gene expression score derived from the gene signature was one of the top-ranked correlates of protection in the NHP vaccine studies. This study aims to bridge preclinical and clinical data with the identification of a gene signature in B cells that is associated with protection from SIV and HIV infection by providing a new approach for evaluating future vaccine candidates.

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Nagy, Gábor, Vittoria Danino, Ulrich Dobrindt, Mark Pallen, Roy Chaudhuri, Levente Emödy, Jay C. Hinton, and Jörg Hacker. "Down-Regulation of Key Virulence Factors Makes the Salmonella enterica Serovar Typhimurium rfaH Mutant a Promising Live-Attenuated Vaccine Candidate." Infection and Immunity 74, no. 10 (October 2006): 5914–25. http://dx.doi.org/10.1128/iai.00619-06.

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ABSTRACT Mutants of Salmonella enterica serovar Typhimurium that lack the transcriptional regulator RfaH are efficient as live oral vaccines against salmonellosis in mice. We show that the attenuation of the vaccine candidate strain is associated with reduced net growth in epithelial and macrophage cells. In order to identify the relevant RfaH-dependent genes, the RfaH regulon was determined with S. enterica serovars Enteritidis and Typhimurium using whole-genome Salmonella microarrays. As well as impacting the expression of genes involved in lipopolysaccharide (LPS) core and O-antigen synthesis, the loss of RfaH results in a marked down-regulation of SPI-4 genes, the flagellum/chemotaxis system, and type III secretion system 1. However, a proportion of these effects could have been the indirect consequence of the altered expression of genes required for LPS biosynthesis. Direct and indirect effects of the rfaH mutation were dissociated by genome-wide transcriptional profiling of a structural deep-rough LPS mutant (waaG). We show that truncation of LPS itself is responsible for the decreased intracellular yield observed for ΔrfaH strains. LPS mutants do not differ in replication ability; rather, they show increased susceptibility to antimicrobial peptides in the intracellular milieu. On the other hand, evidence that deletion of rfaH, as well as some other genes involved in LPS biosynthesis, results in enhanced invasion of various mammalian cells is shown. Exposure of common minor antigens in the absence of serovar-specific antigens might be responsible for the observed cross-reactive nature of the elicited immune response upon vaccination. Increased invasiveness of the Salmonella rfaH mutant into antigen-presenting cells, combined with increased intracellular killing and the potential for raising a cross-protective immune response, renders the rfaH mutant an ideal vaccine candidate.

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Tao, Tao, Mario H. Skiadopoulos, Fatemeh Davoodi, Jeffrey M. Riggs, Peter L. Collins, and Brian R. Murphy. "Replacement of the Ectodomains of the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Recombinant Parainfluenza Virus Type 3 (PIV3) with Their Counterparts from PIV2 Yields Attenuated PIV2 Vaccine Candidates." Journal of Virology 74, no. 14 (July 15, 2000): 6448–58. http://dx.doi.org/10.1128/jvi.74.14.6448-6458.2000.

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ABSTRACT We sought to develop a live attenuated parainfluenza virus type 2 (PIV2) vaccine strain for use in infants and young children, using reverse genetic techniques that previously were used to rapidly produce a live attenuated PIV1 vaccine candidate. The PIV1 vaccine candidate, designated rPIV3-1cp45, was generated by substituting the full-length HN and F proteins of PIV1 for those of PIV3 in the attenuatedcp45 PIV3 vaccine candidate (T. Tao et al., J. Virol. 72:2955–2961, 1998; M. H. Skiadopoulos et al., Vaccine 18:503–510, 1999). However, using the same strategy, we failed to recover recombinant chimeric PIV3-PIV2 isolate carrying the full-length PIV2 glycoproteins in a wild-type PIV3 backbone. Viable PIV3-PIV2 chimeras were recovered when chimeric HN and F open reading frames (ORFs) rather than complete PIV2 F and HN ORFs were used to construct the full-length cDNA. The recovered viruses, designated rPIV3-2CT, in which the PIV2 ectodomain and transmembrane domain were fused to the PIV3 cytoplasmic domain, and rPIV3-2TM, in which the PIV2 ectodomain was fused to the PIV3 transmembrane and cytoplasmic tail domain, possessed similar in vitro and in vivo phenotypes. Thus, it appeared that only the cytoplasmic tail of the HN or F glycoprotein of PIV3 was required for successful recovery of PIV3-PIV2 chimeras. Although rPIV3-2CT and rPIV3-2TM replicated efficiently in vitro, they were moderately to highly attenuated for replication in the respiratory tracts of hamsters, African green monkeys (AGMs), and chimpanzees. This unexpected finding indicated that chimerization of the HN and F proteins of PIV2 and PIV3 itself specified an attenuation phenotype in vivo. Despite this attenuation, these viruses were highly immunogenic and protective against challenge with wild-type PIV2 in hamsters and AGMs, and they represent promising candidates for clinical evaluation as a vaccine against PIV2. These chimeric viruses were further attenuated by the addition of 12 mutations of PIV3cp45 which lie outside of the HN and F genes. The attenuating effects of these mutations were additive with that of the chimerization, and thus inclusion of all or some of the cp45 mutations provides a means to further attenuate the PIV3-PIV2 chimeric vaccine candidates if necessary.

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Ranjit, M. R., and Y. D. Sharma. "Genetic polymorphism of falciparum malaria vaccine candidate antigen genes among field isolates in India." American Journal of Tropical Medicine and Hygiene 61, no. 1 (July 1, 1999): 103–8. http://dx.doi.org/10.4269/ajtmh.1999.61.103.

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Kim, Seon-Hee, Young-An Bae, Ju-Young Seoh, and Hyun-Jong Yang. "Isolation and Characterization of Vaccine Candidate Genes Including CSP and MSP1 in Plasmodium yoelii." Korean Journal of Parasitology 55, no. 3 (June 30, 2017): 255–65. http://dx.doi.org/10.3347/kjp.2017.55.3.255.

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Chenet, Stella M., Lorena L. Tapia, Ananias A. Escalante, Salomon Durand, Carmen Lucas, and David J. Bacon. "Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax." Malaria Journal 11, no. 1 (2012): 68. http://dx.doi.org/10.1186/1475-2875-11-68.

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Min, Ji-Young, Leatrice Vogel, Yumiko Matsuoka, Bin Lu, David Swayne, Hong Jin, George Kemble, and Kanta Subbarao. "A Live Attenuated H7N7 Candidate Vaccine Virus Induces Neutralizing Antibody That Confers Protection from Challenge in Mice, Ferrets, and Monkeys." Journal of Virology 84, no. 22 (September 1, 2010): 11950–60. http://dx.doi.org/10.1128/jvi.01305-10.

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ABSTRACT A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of highly pathogenic (HP) A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (H2N2) virus. The reassortant H7N7 NL/03 ca vaccine virus was temperature sensitive and attenuated in mice, ferrets, and African green monkeys (AGMs). Intranasal (i.n.) administration of a single dose of the H7N7 NL/03 ca vaccine virus fully protected mice from lethal challenge with homologous and heterologous H7 viruses from Eurasian and North American lineages. Two doses of the H7N7 NL/03 ca vaccine induced neutralizing antibodies in serum and provided complete protection from pulmonary replication of homologous and heterologous wild-type H7 challenge viruses in mice and ferrets. One dose of the H7N7 NL/03 ca vaccine elicited an antibody response in one of three AGMs that was completely protected from pulmonary replication of the homologous wild-type H7 challenge virus. The contribution of CD8+ and/or CD4+ T cells to the vaccine-induced protection of mice was evaluated by T-cell depletion; T lymphocytes were not essential for the vaccine-induced protection from lethal challenge with H7 wt viruses. Additionally, passively transferred neutralizing antibody induced by the H7N7 NL/03 ca virus protected mice from lethality following challenge with H7 wt viruses. The safety, immunogenicity, and efficacy of the H7N7 NL/03 ca vaccine virus in mice, ferrets, and AGMs support the evaluation of this vaccine virus in phase I clinical trials.

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Patel, Priyanka, Praveen K. Bharti, Devendra Bansal, Rajive K. Raman, Pradyumna K. Mohapatra, Rakesh Sehgal, Jagadish Mahanta, Ali A. Sultan, and Neeru Singh. "Genetic diversity and antibody responses against Plasmodium falciparum vaccine candidate genes from Chhattisgarh, Central India: Implication for vaccine development." PLOS ONE 12, no. 8 (August 7, 2017): e0182674. http://dx.doi.org/10.1371/journal.pone.0182674.

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Moore, Catrin E., Branwen J. Hennig, Kirsten P. Perrett, J. Claire Hoe, Sue J. Lee, Helen Fletcher, Denise Brocklebank, et al. "Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine." Clinical and Vaccine Immunology 19, no. 3 (December 28, 2011): 295–303. http://dx.doi.org/10.1128/cvi.05379-11.

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ABSTRACTThe rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P= 0.004 [unadjusted]) and CD44 (rs12419062) (P= 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.

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Zhang, Song Lin, Mei Lin Jin, and Huan Chun Chen. "Construction and Vaccine Studies on a Pseudorabies Virus with Deletions in Glycoprotein I and Glycoprotein E Genes." Advanced Materials Research 343-344 (September 2011): 868–74. http://dx.doi.org/10.4028/www.scientific.net/amr.343-344.868.

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A pseudorabies virus (PRV) mutant with deletions in genes for glycoprotein I (gI) and glycoprotein E (gE) was constructed and evaluated as a candidate vaccine strain for its protective by virulent wildtype (wt) PRV Ea strain challenge in pigs. Transfer plasmid pIESE was constructed and co-transfected with PRV genome into IBRS-2 cells to generate a recombinant mutant PRV Ea gI-/gE- virus. The recombinant virus was confirmed by Southern blotting and indirect immunofluorescence assay (IFA). In animal experiments, the immunogenicity was tested by PRV-enzyme-linked immunosorbent assay (ELISA) and PRV neutralizing assay. PRV Ea gI-/gE- elicited significant humoral immune responses to wt PRV Ea, and PRV gI-/gE- immunization protected pigs against a lethal challenge by virulent PRV Ea strain. These results suggested that the recombinant PRV Ea gI-/gE- might be considered as a potential candidate vaccine against PRV.

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Journal articles on the topic 'Vaccine candidate genes'

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