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- Title
The Relationship between RTS,S Vaccine-Induced Antibodies, CD4<sup>+</sup> T Cell Responses and Protection against <i>Plasmodium falciparum</i> Infection.
- Authors
White, Michael T.; Bejon, Philip; Olotu, Ally; Griffin, Jamie T.; Riley, Eleanor M.; Kester, Kent E.; Ockenhouse, Christian F.; Ghani, Azra C.
- Abstract
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.
- Subjects
CD4 antigen; PLASMODIUM falciparum; CIRCUMSPOROZOITE protein; VACCINES; IMMUNOGLOBULINS; VACCINATION; T cells; MALARIA vaccines; ERYTHROCYTES
- Publication
PLoS ONE, 2013, Vol 8, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0061395