title: The relationship between RTS,S vaccine-induced antibodies, CD4⁺ T cell responses and protection against Plasmodium falciparum infection.
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.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom. m.white08@imperial.ac.uk
authors.forename: Michael T
authors.initials: MT
authors.lastname: White
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Ally
authors.initials: A
authors.lastname: Olotu
authors.forename: Jamie T
authors.initials: JT
authors.lastname: Griffin
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins