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A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge
Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386546/ https://www.ncbi.nlm.nih.gov/pubmed/30530620 http://dx.doi.org/10.1128/IAI.00846-18 |
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author | Chan, Win-Yan Entwisle, Claire Ercoli, Giuseppe Ramos-Sevillano, Elise McIlgorm, Ann Cecchini, Paola Bailey, Christopher Lam, Oliver Whiting, Gail Green, Nicola Goldblatt, David Wheeler, Jun X. Brown, Jeremy S. |
author_facet | Chan, Win-Yan Entwisle, Claire Ercoli, Giuseppe Ramos-Sevillano, Elise McIlgorm, Ann Cecchini, Paola Bailey, Christopher Lam, Oliver Whiting, Gail Green, Nicola Goldblatt, David Wheeler, Jun X. Brown, Jeremy S. |
author_sort | Chan, Win-Yan |
collection | PubMed |
description | Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae. |
format | Online Article Text |
id | pubmed-6386546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-63865462019-03-12 A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge Chan, Win-Yan Entwisle, Claire Ercoli, Giuseppe Ramos-Sevillano, Elise McIlgorm, Ann Cecchini, Paola Bailey, Christopher Lam, Oliver Whiting, Gail Green, Nicola Goldblatt, David Wheeler, Jun X. Brown, Jeremy S. Infect Immun Microbial Immunity and Vaccines Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae. American Society for Microbiology 2019-02-21 /pmc/articles/PMC6386546/ /pubmed/30530620 http://dx.doi.org/10.1128/IAI.00846-18 Text en Copyright © 2019 Chan et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Microbial Immunity and Vaccines Chan, Win-Yan Entwisle, Claire Ercoli, Giuseppe Ramos-Sevillano, Elise McIlgorm, Ann Cecchini, Paola Bailey, Christopher Lam, Oliver Whiting, Gail Green, Nicola Goldblatt, David Wheeler, Jun X. Brown, Jeremy S. A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge |
title | A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge |
title_full | A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge |
title_fullStr | A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge |
title_full_unstemmed | A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge |
title_short | A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge |
title_sort | novel, multiple-antigen pneumococcal vaccine protects against lethal streptococcus pneumoniae challenge |
topic | Microbial Immunity and Vaccines |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386546/ https://www.ncbi.nlm.nih.gov/pubmed/30530620 http://dx.doi.org/10.1128/IAI.00846-18 |
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