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Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera
Cholera remains a major public health problem in resource-limited countries. Vaccination is an important strategy to prevent cholera, but currently available vaccines provide only 3 to 5 years of protection. Understanding immune responses to cholera antigens in naturally infected individuals may elu...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092141/ https://www.ncbi.nlm.nih.gov/pubmed/33910997 http://dx.doi.org/10.1128/mSphere.01232-20 |
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author | Kaisar, M. Hasanul Bhuiyan, Mohammed Saruar Akter, Aklima Saleem, Danial Iyer, Anita S. Dash, Pinki Hakim, Al Chowdhury, Fahima Khan, Ashraful Islam Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Charles, Richelle C. Bhuiyan, Taufiqur Rahman |
author_facet | Kaisar, M. Hasanul Bhuiyan, Mohammed Saruar Akter, Aklima Saleem, Danial Iyer, Anita S. Dash, Pinki Hakim, Al Chowdhury, Fahima Khan, Ashraful Islam Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Charles, Richelle C. Bhuiyan, Taufiqur Rahman |
author_sort | Kaisar, M. Hasanul |
collection | PubMed |
description | Cholera remains a major public health problem in resource-limited countries. Vaccination is an important strategy to prevent cholera, but currently available vaccines provide only 3 to 5 years of protection. Understanding immune responses to cholera antigens in naturally infected individuals may elucidate which of these are key to longer-term protection seen following infection. We recently identified Vibrio cholerae O1 sialidase, a neuraminidase that facilitates binding of cholera toxin to intestinal epithelial cells, as immunogenic following infection in two recent high-throughput screens. Here, we present systemic, mucosal, and memory immune responses to sialidase in cholera index cases and evaluated whether systemic responses to sialidase correlated with protection using a cohort of household contacts. Overall, we found age-related differences in antisialidase immune response following cholera. Adults developed significant plasma anti-sialidase IgA, IgG, and IgM responses following infection, whereas older children (≥5 years) developed both IgG and IgM responses, and younger children only developed IgM responses. Neither older children nor younger children had a rise in IgA responses over the convalescent phase of infection (day 7/day 30). On evaluation of mucosal responses and memory B-cell responses to sialidase, we found adults developed IgA antibody-secreting cell (ASC) and memory B-cell responses. Finally, in household contacts, the presence of serum anti-sialidase IgA, IgG, and IgM antibodies at enrollment was associated with a decrease in the risk of subsequent infection. These data show cholera patients develop age-related immune responses against sialidase and suggest that immune responses that target sialidase may contribute to protective immunity against cholera. IMPORTANCE Cholera infection can result in severe dehydration that may lead to death within a short period of time if not treated immediately. Vaccination is an important strategy to prevent the disease. Oral cholera vaccines provide 3 to 5 years of protection, with 60% protective efficacy, while natural infection provides longer-term protection than vaccination. Understanding the immune responses after natural infection is important to better understand immune responses to antigens that mediate longer-term protection. Sialidase is a neuraminidase that facilitates binding of cholera toxin to intestinal epithelial cells. We show here that patients with cholera develop systemic, mucosal, and memory B-cell immune responses to the sialidase antigen of Vibrio cholerae O1 and that plasma responses targeting this antigen correlate with protection. |
format | Online Article Text |
id | pubmed-8092141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80921412021-05-11 Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera Kaisar, M. Hasanul Bhuiyan, Mohammed Saruar Akter, Aklima Saleem, Danial Iyer, Anita S. Dash, Pinki Hakim, Al Chowdhury, Fahima Khan, Ashraful Islam Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Charles, Richelle C. Bhuiyan, Taufiqur Rahman mSphere Research Article Cholera remains a major public health problem in resource-limited countries. Vaccination is an important strategy to prevent cholera, but currently available vaccines provide only 3 to 5 years of protection. Understanding immune responses to cholera antigens in naturally infected individuals may elucidate which of these are key to longer-term protection seen following infection. We recently identified Vibrio cholerae O1 sialidase, a neuraminidase that facilitates binding of cholera toxin to intestinal epithelial cells, as immunogenic following infection in two recent high-throughput screens. Here, we present systemic, mucosal, and memory immune responses to sialidase in cholera index cases and evaluated whether systemic responses to sialidase correlated with protection using a cohort of household contacts. Overall, we found age-related differences in antisialidase immune response following cholera. Adults developed significant plasma anti-sialidase IgA, IgG, and IgM responses following infection, whereas older children (≥5 years) developed both IgG and IgM responses, and younger children only developed IgM responses. Neither older children nor younger children had a rise in IgA responses over the convalescent phase of infection (day 7/day 30). On evaluation of mucosal responses and memory B-cell responses to sialidase, we found adults developed IgA antibody-secreting cell (ASC) and memory B-cell responses. Finally, in household contacts, the presence of serum anti-sialidase IgA, IgG, and IgM antibodies at enrollment was associated with a decrease in the risk of subsequent infection. These data show cholera patients develop age-related immune responses against sialidase and suggest that immune responses that target sialidase may contribute to protective immunity against cholera. IMPORTANCE Cholera infection can result in severe dehydration that may lead to death within a short period of time if not treated immediately. Vaccination is an important strategy to prevent the disease. Oral cholera vaccines provide 3 to 5 years of protection, with 60% protective efficacy, while natural infection provides longer-term protection than vaccination. Understanding the immune responses after natural infection is important to better understand immune responses to antigens that mediate longer-term protection. Sialidase is a neuraminidase that facilitates binding of cholera toxin to intestinal epithelial cells. We show here that patients with cholera develop systemic, mucosal, and memory B-cell immune responses to the sialidase antigen of Vibrio cholerae O1 and that plasma responses targeting this antigen correlate with protection. American Society for Microbiology 2021-04-28 /pmc/articles/PMC8092141/ /pubmed/33910997 http://dx.doi.org/10.1128/mSphere.01232-20 Text en Copyright © 2021 Kaisar 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 Kaisar, M. Hasanul Bhuiyan, Mohammed Saruar Akter, Aklima Saleem, Danial Iyer, Anita S. Dash, Pinki Hakim, Al Chowdhury, Fahima Khan, Ashraful Islam Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Charles, Richelle C. Bhuiyan, Taufiqur Rahman Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera |
title | Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera |
title_full | Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera |
title_fullStr | Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera |
title_full_unstemmed | Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera |
title_short | Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera |
title_sort | vibrio cholerae sialidase-specific immune responses are associated with protection against cholera |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092141/ https://www.ncbi.nlm.nih.gov/pubmed/33910997 http://dx.doi.org/10.1128/mSphere.01232-20 |
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