The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection

Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4+ T cells specific for the circumsporozoite protein (CSP). Using a biologically-motivated mathematical model of sporozoite infection fitted to data from malaria-naive adults vaccinated with RTS,S and...

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Main Authors:	White, Michael T., Bejon, Philip, Olotu, Ally, Griffin, Jamie T., Riley, Eleanor M., Kester, Kent E., Ockenhouse, Christian F., Ghani, Azra C.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628884/

id	pubmed-3628884
recordtype	oai_dc
spelling	pubmed-36288842013-04-23 The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection White, Michael T. Bejon, Philip Olotu, Ally Griffin, Jamie T. Riley, Eleanor M. Kester, Kent E. Ockenhouse, Christian F. Ghani, Azra C. Research Article Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4+ T cells specific for the circumsporozoite protein (CSP). Using a biologically-motivated mathematical model of sporozoite infection fitted to data from malaria-naive adults vaccinated with RTS,S and subjected to experimental P. falciparum challenge, we characterised the relationship between antibodies, CD4+ T cell responses and protection from infection. Both anti-CSP antibody titres and CSP-specific CD4+ T cells were identified as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32% (95% confidence interval (CI) 24%–41%) of infections. The addition of RTS,S-induced CSP-specific CD4+ T cells was estimated to increase vaccine efficacy against infection to 40% (95% CI, 34%–48%). This protective efficacy is estimated to result from a 96.1% (95% CI, 93.4%–97.8%) reduction in the liver-to-blood parasite inoculum, indicating that in volunteers who developed P. falciparum infection, a small number of parasites (often the progeny of a single surviving sporozoite) are responsible for breakthrough blood-stage infections. Public Library of Science 2013-04-16 /pmc/articles/PMC3628884/ /pubmed/23613845 http://dx.doi.org/10.1371/journal.pone.0061395 Text en © 2013 White et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	White, Michael T. Bejon, Philip Olotu, Ally Griffin, Jamie T. Riley, Eleanor M. Kester, Kent E. Ockenhouse, Christian F. Ghani, Azra C.
spellingShingle	White, Michael T. Bejon, Philip Olotu, Ally Griffin, Jamie T. Riley, Eleanor M. Kester, Kent E. Ockenhouse, Christian F. Ghani, Azra C. The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection
author_facet	White, Michael T. Bejon, Philip Olotu, Ally Griffin, Jamie T. Riley, Eleanor M. Kester, Kent E. Ockenhouse, Christian F. Ghani, Azra C.
author_sort	White, Michael T.
title	The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection
title_short	The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection
title_full	The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection
title_fullStr	The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection
title_full_unstemmed	The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection
title_sort	relationship between rts,s vaccine-induced antibodies, cd4+ t cell responses and protection against plasmodium falciparum infection
description	Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4+ T cells specific for the circumsporozoite protein (CSP). Using a biologically-motivated mathematical model of sporozoite infection fitted to data from malaria-naive adults vaccinated with RTS,S and subjected to experimental P. falciparum challenge, we characterised the relationship between antibodies, CD4+ T cell responses and protection from infection. Both anti-CSP antibody titres and CSP-specific CD4+ T cells were identified as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32% (95% confidence interval (CI) 24%–41%) of infections. The addition of RTS,S-induced CSP-specific CD4+ T cells was estimated to increase vaccine efficacy against infection to 40% (95% CI, 34%–48%). This protective efficacy is estimated to result from a 96.1% (95% CI, 93.4%–97.8%) reduction in the liver-to-blood parasite inoculum, indicating that in volunteers who developed P. falciparum infection, a small number of parasites (often the progeny of a single surviving sporozoite) are responsible for breakthrough blood-stage infections.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628884/
_version_	1611970770097930240

The Relationship between RTS,S Vaccine-Induced Antibodies, CD4+ T Cell Responses and Protection against Plasmodium falciparum Infection

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