- Comment in:
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Lancet. 2004 Oct 16-22;364(9443):1380-3.
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Lancet. 2005 Feb 5-11;365(9458):472-3.
Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial.
Alonso PL,
Sacarlal J,
Aponte JJ,
Leach A,
Macete E,
Milman J,
Mandomando I,
Spiessens B,
Guinovart C,
Espasa M,
Bassat Q,
Aide P,
Ofori-Anyinam O,
Navia MM,
Corachan S,
Ceuppens M,
Dubois MC,
Demoitié MA,
Dubovsky F,
Menéndez C,
Tornieporth N,
Ballou WR,
Thompson R,
Cohen J.
Centre de Salut Internacional, Hospital Clínic/IDIBAPS, Universitat de Barcelona, Barcelona, Spain. palonso@clinic.ub.es
BACKGROUND: Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess vaccine efficacy, immunogenicity, and safety in young African children. METHODS: We did a double-blind, phase IIb, randomised controlled trial in Mozambique in 2022 children aged 1-4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature > or =37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417). Analysis was per protocol. FINDINGS: 115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per-protocol analysis. Vaccine efficacy for the first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37% lower in the RTS,S/AS02A group compared with the control group (11.9% vs 18.9%; p=0.0003). Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In cohort 2, vaccine efficacy for extending time to first infection was 45.0% (31.4-55.9; p<0.0001). INTERPRETATION: The RTS,S/AS02A vaccine was safe, well tolerated, and immunogenic. Our results show development of an effective vaccine against malaria is feasible.
PMID: 15488216 [PubMed - indexed for MEDLINE]