Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans.
The four serotypes of dengue virus (DENV) cause dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Severe disease has been associated with heterotypic secondary DENV infection, mediated by cross-reactive antibodies (Abs) and/or cross-reactive T cells. The role of cross-r...
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ftdoajarticles:oai:doaj.org/article:d80e277ce2a649ddb1d184ad194aa2ea 2023-05-15T15:15:42+02:00 Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. Simona Zompi Magelda Montoya Marie O Pohl Angel Balmaseda Eva Harris 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001568 https://doaj.org/article/d80e277ce2a649ddb1d184ad194aa2ea EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3308930?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001568 https://doaj.org/article/d80e277ce2a649ddb1d184ad194aa2ea PLoS Neglected Tropical Diseases, Vol 6, Iss 3, p e1568 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001568 2022-12-30T22:25:04Z The four serotypes of dengue virus (DENV) cause dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Severe disease has been associated with heterotypic secondary DENV infection, mediated by cross-reactive antibodies (Abs) and/or cross-reactive T cells. The role of cross-reactive immunity in mediating enhanced disease versus cross-protection against secondary heterotypic DENV infection is not well defined. A better understanding of the cross-reactive immune response in natural infections is critical for development of safe and effective tetravalent vaccines. We studied the B cell phenotype of circulating B cells in the blood of pediatric patients suspected of dengue during the 2010-2011 dengue season in Managua, Nicaragua (n = 216), which was dominated by the DENV-3 serotype. We found a markedly larger percentage of plasmablast/plasma cells (PB/PCs) circulating in DENV-positive patients as compared to patients with Other Febrile Illnesses (OFIs). The percentage of DENV-specific PB/PCs against DENV-3 represented 10% of the circulating antibody-producing cells (ASCs) in secondary DENV-3 infections. Importantly, the cross-reactive DENV-specific B cell response was higher against a heterotypic serotype, with 46% of circulating PB/PCs specific to DENV-2 and 10% specific to DENV-3 during acute infection. We also observed a higher cross-reactive DENV-specific IgG serum avidity directed against DENV-2 as compared to DENV-3 during acute infection. The neutralization capacity of the serum was broadly cross-reactive against the four DENV serotypes both during the acute phase and at 3 months post-onset of symptoms. Overall, the cross-reactive B cell immune response dominates during secondary DENV infections in humans. These results reflect our recent findings in a mouse model of DENV cross-protection. In addition, this study enabled the development of increased technical and research capacity of Nicaraguan scientists and the implementation of several new immunological assays in the field. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 3 e1568 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Simona Zompi Magelda Montoya Marie O Pohl Angel Balmaseda Eva Harris Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The four serotypes of dengue virus (DENV) cause dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Severe disease has been associated with heterotypic secondary DENV infection, mediated by cross-reactive antibodies (Abs) and/or cross-reactive T cells. The role of cross-reactive immunity in mediating enhanced disease versus cross-protection against secondary heterotypic DENV infection is not well defined. A better understanding of the cross-reactive immune response in natural infections is critical for development of safe and effective tetravalent vaccines. We studied the B cell phenotype of circulating B cells in the blood of pediatric patients suspected of dengue during the 2010-2011 dengue season in Managua, Nicaragua (n = 216), which was dominated by the DENV-3 serotype. We found a markedly larger percentage of plasmablast/plasma cells (PB/PCs) circulating in DENV-positive patients as compared to patients with Other Febrile Illnesses (OFIs). The percentage of DENV-specific PB/PCs against DENV-3 represented 10% of the circulating antibody-producing cells (ASCs) in secondary DENV-3 infections. Importantly, the cross-reactive DENV-specific B cell response was higher against a heterotypic serotype, with 46% of circulating PB/PCs specific to DENV-2 and 10% specific to DENV-3 during acute infection. We also observed a higher cross-reactive DENV-specific IgG serum avidity directed against DENV-2 as compared to DENV-3 during acute infection. The neutralization capacity of the serum was broadly cross-reactive against the four DENV serotypes both during the acute phase and at 3 months post-onset of symptoms. Overall, the cross-reactive B cell immune response dominates during secondary DENV infections in humans. These results reflect our recent findings in a mouse model of DENV cross-protection. In addition, this study enabled the development of increased technical and research capacity of Nicaraguan scientists and the implementation of several new immunological assays in the field. |
format |
Article in Journal/Newspaper |
author |
Simona Zompi Magelda Montoya Marie O Pohl Angel Balmaseda Eva Harris |
author_facet |
Simona Zompi Magelda Montoya Marie O Pohl Angel Balmaseda Eva Harris |
author_sort |
Simona Zompi |
title |
Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. |
title_short |
Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. |
title_full |
Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. |
title_fullStr |
Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. |
title_full_unstemmed |
Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. |
title_sort |
dominant cross-reactive b cell response during secondary acute dengue virus infection in humans. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001568 https://doaj.org/article/d80e277ce2a649ddb1d184ad194aa2ea |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 3, p e1568 (2012) |
op_relation |
http://europepmc.org/articles/PMC3308930?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001568 https://doaj.org/article/d80e277ce2a649ddb1d184ad194aa2ea |
op_doi |
https://doi.org/10.1371/journal.pntd.0001568 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
6 |
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3 |
container_start_page |
e1568 |
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1766346049914404864 |