The relationship between RTS,S vaccine-induced antibodies, CD4⁺ T cell responses and protection against Plasmodium falciparum infection

• Published in: PloS one 2013-04, Vol.8 (4), p.e61395-e61395
• 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: Article
• Language: English
• Subjects: Adult; Adults; Animals; Anopheles; Antibodies; Antibodies, Protozoan - immunology; Biology; Blood; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; Circumsporozoite protein; Confidence intervals; Culicidae; Drug dosages; Epidemiology; Female; Humans; Hygiene; Immunoglobulins; Immunology; Infections; Infectious diseases; Inoculum; Liver; Lymphocytes; Lymphocytes T; Malaria; Malaria Vaccines - immunology; Malaria, Falciparum - immunology; Malaria, Falciparum - prevention & control; Male; Mathematical models; Medical research; Medicine; Mosquitoes; Parasites; Plasmodium; Plasmodium falciparum; Plasmodium falciparum - immunology; Plasmodium falciparum - pathogenicity; Progeny; Protozoan Proteins - immunology; Tropical diseases; Vaccination; Vaccine efficacy; Vaccines; Vector-borne diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0061395

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.