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Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry
There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children ca...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529421/ https://www.ncbi.nlm.nih.gov/pubmed/37400283 http://dx.doi.org/10.1016/j.vaccine.2023.06.052 |
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author | Kelly, Meagan Mandlik, Anjali Charles, Richelle C. Verma, Smriti Calderwood, Stephen B. Leung, Daniel T. Biswas, Rajib Islam, Kamrul Kamruzzaman, Mohammad Chowdhury, Fahima Khanam, Farhana Vann, Willie F. Khan, Ashraful Islam Bhuiyan, Taufiqur Rahman Qadri, Firdausi Vortherms, Anthony R. Kaminski, Robert Kováč, Pavol Xu, Peng Ryan, Edward T. |
author_facet | Kelly, Meagan Mandlik, Anjali Charles, Richelle C. Verma, Smriti Calderwood, Stephen B. Leung, Daniel T. Biswas, Rajib Islam, Kamrul Kamruzzaman, Mohammad Chowdhury, Fahima Khanam, Farhana Vann, Willie F. Khan, Ashraful Islam Bhuiyan, Taufiqur Rahman Qadri, Firdausi Vortherms, Anthony R. Kaminski, Robert Kováč, Pavol Xu, Peng Ryan, Edward T. |
author_sort | Kelly, Meagan |
collection | PubMed |
description | There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children can be problematic, but high level and durable responses can be induced by presenting polysaccharides conjugated to carrier proteins. An effective shigella vaccine will need to be multivalent, targeting the most common global species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. Here we report the development of shigella conjugate vaccines (SCV) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using squaric acid chemistry to result in single point sun-burst type display of OSP from carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. We confirmed structure and demonstrated that these conjugates were recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG responses, as well as rTTHc-specific IgG responses. Vaccination induced serotype-specific bactericidal antibody responses against S. flexneri, and vaccinated animals were protected against keratoconjunctivitis (Sereny test) and intraperitoneal challenge with virulent S. flexneri 2a and 3a, respectively. Our results support further development of this platform conjugation technology in the development of shigella conjugate vaccines for use in resource-limited settings. |
format | Online Article Text |
id | pubmed-10529421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-105294212023-09-27 Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry Kelly, Meagan Mandlik, Anjali Charles, Richelle C. Verma, Smriti Calderwood, Stephen B. Leung, Daniel T. Biswas, Rajib Islam, Kamrul Kamruzzaman, Mohammad Chowdhury, Fahima Khanam, Farhana Vann, Willie F. Khan, Ashraful Islam Bhuiyan, Taufiqur Rahman Qadri, Firdausi Vortherms, Anthony R. Kaminski, Robert Kováč, Pavol Xu, Peng Ryan, Edward T. Vaccine Article There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children can be problematic, but high level and durable responses can be induced by presenting polysaccharides conjugated to carrier proteins. An effective shigella vaccine will need to be multivalent, targeting the most common global species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. Here we report the development of shigella conjugate vaccines (SCV) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using squaric acid chemistry to result in single point sun-burst type display of OSP from carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. We confirmed structure and demonstrated that these conjugates were recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG responses, as well as rTTHc-specific IgG responses. Vaccination induced serotype-specific bactericidal antibody responses against S. flexneri, and vaccinated animals were protected against keratoconjunctivitis (Sereny test) and intraperitoneal challenge with virulent S. flexneri 2a and 3a, respectively. Our results support further development of this platform conjugation technology in the development of shigella conjugate vaccines for use in resource-limited settings. 2023-07-31 2023-07-01 /pmc/articles/PMC10529421/ /pubmed/37400283 http://dx.doi.org/10.1016/j.vaccine.2023.06.052 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Kelly, Meagan Mandlik, Anjali Charles, Richelle C. Verma, Smriti Calderwood, Stephen B. Leung, Daniel T. Biswas, Rajib Islam, Kamrul Kamruzzaman, Mohammad Chowdhury, Fahima Khanam, Farhana Vann, Willie F. Khan, Ashraful Islam Bhuiyan, Taufiqur Rahman Qadri, Firdausi Vortherms, Anthony R. Kaminski, Robert Kováč, Pavol Xu, Peng Ryan, Edward T. Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry |
title | Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry |
title_full | Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry |
title_fullStr | Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry |
title_full_unstemmed | Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry |
title_short | Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry |
title_sort | development of shigella conjugate vaccines targeting shigella flexneri 2a and s. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529421/ https://www.ncbi.nlm.nih.gov/pubmed/37400283 http://dx.doi.org/10.1016/j.vaccine.2023.06.052 |
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