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A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies
Streptococcus pneumoniae (Spn) remains a major cause of global mortality, with extensive antigenic diversity between capsular serotypes that poses an ongoing challenge for vaccine development. Widespread use of pneumococcal conjugate vaccines (PCVs) targeting Spn capsules has greatly reduced infecti...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600166/ https://www.ncbi.nlm.nih.gov/pubmed/36125268 http://dx.doi.org/10.1128/mbio.02367-22 |
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author | David, Shannon C. Brazel, Erin B. Singleton, Eve V. Minhas, Vikrant Laan, Zoe Scougall, Catherine Chen, Austen Y. Wang, Hui Gates, Chloe J. McLean, Kimberley T. Brown, Jeremy S. Ercoli, Giuseppe Higgins, Rachel A. Licciardi, Paul V. Mulholland, Kim Davies, Justin B. Hirst, Timothy R. Paton, James C. Alsharifi, Mohammed |
author_facet | David, Shannon C. Brazel, Erin B. Singleton, Eve V. Minhas, Vikrant Laan, Zoe Scougall, Catherine Chen, Austen Y. Wang, Hui Gates, Chloe J. McLean, Kimberley T. Brown, Jeremy S. Ercoli, Giuseppe Higgins, Rachel A. Licciardi, Paul V. Mulholland, Kim Davies, Justin B. Hirst, Timothy R. Paton, James C. Alsharifi, Mohammed |
author_sort | David, Shannon C. |
collection | PubMed |
description | Streptococcus pneumoniae (Spn) remains a major cause of global mortality, with extensive antigenic diversity between capsular serotypes that poses an ongoing challenge for vaccine development. Widespread use of pneumococcal conjugate vaccines (PCVs) targeting Spn capsules has greatly reduced infections by vaccine-included serotypes but has led to increased infections by nonincluded serotypes. To date, high cost of PCVs has also limited their usefulness in low-income regions where disease burdens are highest. To overcome these limitations, serotype-independent vaccines are being actively researched. We have developed a whole-cell gamma-irradiated Spn vaccine (termed Gamma-PN) providing serotype-independent protection. We demonstrate that Gamma-PN immunization of mice or rabbits via the clinically relevant intramuscular route induces protein-specific antibodies able to bind numerous nonvaccine encapsulated serotypes, which mediate opsonophagocytic killing and protection against lethal challenges. Gamma-PN induced comparable or superior opsonophagocytic killing assay (OPKA) responses in rabbits to the licensed Prevnar 13 vaccine (PCV13) for vaccine-included serotypes, and a superior response to nonincluded serotypes, including emergent 22F and 35B. Additionally, despite a lower observed reactogenicity, administration of Gamma-PN without adjuvant resulted in higher OPKA responses and improved protection compared to adjuvanted Gamma-PN. To our knowledge, this has not been demonstrated previously for a whole-inactivated Spn vaccine. Eliminating the requirement for adjuvant comes with numerous benefits for clinical applications of this vaccine and poses interesting questions for the inclusion of adjuvant in similar vaccines in development. |
format | Online Article Text |
id | pubmed-9600166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-96001662022-10-27 A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies David, Shannon C. Brazel, Erin B. Singleton, Eve V. Minhas, Vikrant Laan, Zoe Scougall, Catherine Chen, Austen Y. Wang, Hui Gates, Chloe J. McLean, Kimberley T. Brown, Jeremy S. Ercoli, Giuseppe Higgins, Rachel A. Licciardi, Paul V. Mulholland, Kim Davies, Justin B. Hirst, Timothy R. Paton, James C. Alsharifi, Mohammed mBio Research Article Streptococcus pneumoniae (Spn) remains a major cause of global mortality, with extensive antigenic diversity between capsular serotypes that poses an ongoing challenge for vaccine development. Widespread use of pneumococcal conjugate vaccines (PCVs) targeting Spn capsules has greatly reduced infections by vaccine-included serotypes but has led to increased infections by nonincluded serotypes. To date, high cost of PCVs has also limited their usefulness in low-income regions where disease burdens are highest. To overcome these limitations, serotype-independent vaccines are being actively researched. We have developed a whole-cell gamma-irradiated Spn vaccine (termed Gamma-PN) providing serotype-independent protection. We demonstrate that Gamma-PN immunization of mice or rabbits via the clinically relevant intramuscular route induces protein-specific antibodies able to bind numerous nonvaccine encapsulated serotypes, which mediate opsonophagocytic killing and protection against lethal challenges. Gamma-PN induced comparable or superior opsonophagocytic killing assay (OPKA) responses in rabbits to the licensed Prevnar 13 vaccine (PCV13) for vaccine-included serotypes, and a superior response to nonincluded serotypes, including emergent 22F and 35B. Additionally, despite a lower observed reactogenicity, administration of Gamma-PN without adjuvant resulted in higher OPKA responses and improved protection compared to adjuvanted Gamma-PN. To our knowledge, this has not been demonstrated previously for a whole-inactivated Spn vaccine. Eliminating the requirement for adjuvant comes with numerous benefits for clinical applications of this vaccine and poses interesting questions for the inclusion of adjuvant in similar vaccines in development. American Society for Microbiology 2022-09-20 /pmc/articles/PMC9600166/ /pubmed/36125268 http://dx.doi.org/10.1128/mbio.02367-22 Text en Copyright © 2022 David 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 | Research Article David, Shannon C. Brazel, Erin B. Singleton, Eve V. Minhas, Vikrant Laan, Zoe Scougall, Catherine Chen, Austen Y. Wang, Hui Gates, Chloe J. McLean, Kimberley T. Brown, Jeremy S. Ercoli, Giuseppe Higgins, Rachel A. Licciardi, Paul V. Mulholland, Kim Davies, Justin B. Hirst, Timothy R. Paton, James C. Alsharifi, Mohammed A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies |
title | A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies |
title_full | A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies |
title_fullStr | A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies |
title_full_unstemmed | A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies |
title_short | A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies |
title_sort | nonadjuvanted whole-inactivated pneumococcal vaccine induces multiserotype opsonophagocytic responses mediated by noncapsule-specific antibodies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600166/ https://www.ncbi.nlm.nih.gov/pubmed/36125268 http://dx.doi.org/10.1128/mbio.02367-22 |
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