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PROTECTIVE EFFICACY OF THE RTS,S/AS02 PLASMODIUM FALCIPARUM MALARIA VACCINE IS NOT STRAIN SPECIFIC

RTS,S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein (CSP) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen. It has been shown to induce significant protection to challenge infection with a homologous parasite strain in American volunteers. In a recently completed trial in semi-immune Gambian adults, vaccine efficacy against natural infection was 34% (95% confidence interval = 8–53%, P = 0.014) during the malaria season following vaccination. Breakthrough P. falciparum parasites sampled from vaccinated subjects and from controls were genotyped at two polymorphic regions of the csp gene encoding T cell epitopes (csp-th2r and csp-th3r) to determine if the vaccine conferred a strain-specific effect. The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups. Also, the mean number of genotypes per infection in the RTS,S/AS02 group was not reduced compared with the controls.

Received January 28, 2002. Accepted for publication April 29, 2002.

Acknowledgments: We thank the volunteers who participated in this study and the field staff of the Medical Research Council laboratories for their assistance with blood collection and slide reading. We are also grateful to Professors Adrian Hill and Geoffrey Targett for useful discussions.

Financial support: This study was funded by a European Economic Community (EEC) grant (PL 962164).

This research was funded by an EEC grant (PI 962164) for which GlaxoSmithKline Biologicals was the coordinator. Drs. Nadia Tornieporth and Joe Cohen are employees of GlaxoSmithKline Biologicals.

Reprint requests: Ali Alloueche, Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, Telephone: 44-20-7927-2338, Fax: 44-20-7636-8739, Email: ali.alloueche{at}lshtm.ac.uk

Authors’ addresses: Ali Alloueche, David J. Conway, and Brian M. Greenwood, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT. United Kingdom, Telephone: 44-20-7927-2338/2326, Fax: 44-20-7636-8739, E-mail: Ali.Alloueche{at}lshtm.ac.uk. Paul Milligan, Margaret Pinder, Kalifa Bojang, and Tom Doherty, Medical Research Council Laboratories, P.O. Box 273, Fajara, The Gambia. Nadia Tornieporth and Joe Cohen, GlaxoSmith-Kline Biologicals, Rue de l’Institut, B-1330, Rixensart, Belgium.

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