SAFETY, IMMUNOGENICITY AND LIMITED EFFICACY STUDY OF A RECOMBINANT PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE VACCINE IN THAI SOLDIERS

Thai soldiers were vaccinated with a recombinant protein derived from the central repeat region of the circumsporozoite (CS) protein of Plas modium falciparum conjugated to Toxin A (detoxified) of Pseudomonas ae ruginosa (R32Tox-A) to evaluate its safety, immunogenicity and efficac y. In a randomized, double-blind manner, 199 volunteers received eithe r R32Tox-A or a control vaccine at 0, 8 and 16 weeks. Immunization was preformed in a malaria non-transmission area, after completion of whi ch volunteers were deployed to an endemic border area and monitored cl osely to allow early detection and treatment of infection. The vaccine was found to be safe and to elicit antibody responses in all vaccinee s. Peak CS antibody (IgG) concentrations in malaria-experienced vaccin ees exceeded those in malaria-naive vaccinees (mean 40.6 versus 16.1 m u g ml(-1); p = 0.005) as well as those induced by previous CS protein -derived vaccines and observed in association with natural infections. A log-rank comparison of time to falciparum malaria revealed no diffe rences between vaccinated and non-vaccinated subjects. Secondary analy ses revealed that CS antibody levels were lower in vaccinee malaria ca ses than in non-cases, 3 and 5 months after the third dose of vaccine (p = 0.06 and p = 0.014, respectively). Because antibody levels had fa llen substantially before peak malaria transmission occurred the quest ion of whether high levels of cs antibody are protective remains to be resolved.