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Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine
It has been estimated that more than 390 million people are infected with Dengue virus every year; around 96 millions of these infections result in clinical pathologies. To date, there is only one licensed viral vector-based Dengue virus vaccine CYD-TDV approved for use in dengue endemic areas. Whil...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809550/ https://www.ncbi.nlm.nih.gov/pubmed/35061851 http://dx.doi.org/10.1371/journal.ppat.1009903 |
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author | Izmirly, Abdullah M. Pelletier, Adam-Nicolas Connors, Jennifer Taramangalam, Bhavani Alturki, Sawsan O. Gordon, Emma A. Alturki, Sana O. Mell, Joshua C. Swaminathan, Gokul Karthik, Vivin Kutzler, Michele A. Kallas, Esper G. Sekaly, Rafick-Pierre Haddad, Elias K. |
author_facet | Izmirly, Abdullah M. Pelletier, Adam-Nicolas Connors, Jennifer Taramangalam, Bhavani Alturki, Sawsan O. Gordon, Emma A. Alturki, Sana O. Mell, Joshua C. Swaminathan, Gokul Karthik, Vivin Kutzler, Michele A. Kallas, Esper G. Sekaly, Rafick-Pierre Haddad, Elias K. |
author_sort | Izmirly, Abdullah M. |
collection | PubMed |
description | It has been estimated that more than 390 million people are infected with Dengue virus every year; around 96 millions of these infections result in clinical pathologies. To date, there is only one licensed viral vector-based Dengue virus vaccine CYD-TDV approved for use in dengue endemic areas. While initially approved for administration independent of serostatus, the current guidance only recommends the use of this vaccine for seropositive individuals. Therefore, there is a critical need for investigating the influence of Dengue virus serostatus and immunological mechanisms that influence vaccine outcome. Here, we provide comprehensive evaluation of sero-status and host immune factors that correlate with robust immune responses to a Dengue virus vector based tetravalent vaccine (TV003) in a Phase II clinical cohort of human participants. We observed that sero-positive individuals demonstrate a much stronger immune response to the TV003 vaccine. Our multi-layered immune profiling revealed that sero-positive subjects have increased baseline/pre-vaccination frequencies of circulating T follicular helper (cTfh) cells and the Tfh related chemokine CXCL13/BLC. Importantly, this baseline/pre-vaccination cTfh profile correlated with the vaccinees’ ability to launch neutralizing antibody response against all four sero-types of Dengue virus, an important endpoint for Dengue vaccine clinical trials. Overall, we provide novel insights into the favorable cTfh related immune status that persists in Dengue virus sero-positive individuals that correlate with their ability to mount robust vaccine specific immune responses. Such detailed interrogation of cTfh cell biology in the context of clinical vaccinology will help uncover mechanisms and targets for favorable immuno-modulatory agents. |
format | Online Article Text |
id | pubmed-8809550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88095502022-02-03 Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine Izmirly, Abdullah M. Pelletier, Adam-Nicolas Connors, Jennifer Taramangalam, Bhavani Alturki, Sawsan O. Gordon, Emma A. Alturki, Sana O. Mell, Joshua C. Swaminathan, Gokul Karthik, Vivin Kutzler, Michele A. Kallas, Esper G. Sekaly, Rafick-Pierre Haddad, Elias K. PLoS Pathog Research Article It has been estimated that more than 390 million people are infected with Dengue virus every year; around 96 millions of these infections result in clinical pathologies. To date, there is only one licensed viral vector-based Dengue virus vaccine CYD-TDV approved for use in dengue endemic areas. While initially approved for administration independent of serostatus, the current guidance only recommends the use of this vaccine for seropositive individuals. Therefore, there is a critical need for investigating the influence of Dengue virus serostatus and immunological mechanisms that influence vaccine outcome. Here, we provide comprehensive evaluation of sero-status and host immune factors that correlate with robust immune responses to a Dengue virus vector based tetravalent vaccine (TV003) in a Phase II clinical cohort of human participants. We observed that sero-positive individuals demonstrate a much stronger immune response to the TV003 vaccine. Our multi-layered immune profiling revealed that sero-positive subjects have increased baseline/pre-vaccination frequencies of circulating T follicular helper (cTfh) cells and the Tfh related chemokine CXCL13/BLC. Importantly, this baseline/pre-vaccination cTfh profile correlated with the vaccinees’ ability to launch neutralizing antibody response against all four sero-types of Dengue virus, an important endpoint for Dengue vaccine clinical trials. Overall, we provide novel insights into the favorable cTfh related immune status that persists in Dengue virus sero-positive individuals that correlate with their ability to mount robust vaccine specific immune responses. Such detailed interrogation of cTfh cell biology in the context of clinical vaccinology will help uncover mechanisms and targets for favorable immuno-modulatory agents. Public Library of Science 2022-01-21 /pmc/articles/PMC8809550/ /pubmed/35061851 http://dx.doi.org/10.1371/journal.ppat.1009903 Text en © 2022 Izmirly et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Izmirly, Abdullah M. Pelletier, Adam-Nicolas Connors, Jennifer Taramangalam, Bhavani Alturki, Sawsan O. Gordon, Emma A. Alturki, Sana O. Mell, Joshua C. Swaminathan, Gokul Karthik, Vivin Kutzler, Michele A. Kallas, Esper G. Sekaly, Rafick-Pierre Haddad, Elias K. Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine |
title | Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine |
title_full | Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine |
title_fullStr | Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine |
title_full_unstemmed | Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine |
title_short | Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine |
title_sort | pre-vaccination frequency of circulatory tfh is associated with robust immune response to tv003 dengue vaccine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809550/ https://www.ncbi.nlm.nih.gov/pubmed/35061851 http://dx.doi.org/10.1371/journal.ppat.1009903 |
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