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

PLoS One. 2013 Apr 16;8(4):e61395. doi: 10.1371/journal.pone.0061395. Print 2013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Protozoan / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Female
  • Humans
  • Malaria Vaccines / immunology
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control*
  • Male
  • Plasmodium falciparum / immunology*
  • Plasmodium falciparum / pathogenicity
  • Protozoan Proteins / immunology


  • Antibodies, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins