A PRELIMINARY EVALUATION OF A RECOMBINANT CIRCUMSPOROZOITE PROTEIN VACCINE AGAINST PLASMODIUM-FALCIPARUM MALARIA

Background The candidate vaccines against malaria are poorly immunogen ic and thus have been ineffective in preventing infection. We develope d a vaccine based on the circumsporozoite protein of Plasmodium falcip arum that incorporates adjuvants selected to enhance the immune respon se. Methods The antigen consists of a hybrid in which the circumsporoz oite protein fused to hepatitis B surface antigen (HBsAg) is expressed together with unfused HBsAg. We evaluated three formulations of this antigen in an unblinded trial in 46 subjects who had never been expose d to malaria. Results Two of the vaccine formulations were highly immu nogenic. Four subjects had adverse systemic reactions that may have re sulted from the intensity of the immune response after the second dose , which led us to reduce the third dose. Twenty-two vaccinated subject s and six unimmunized controls under went a challenge consisting of bi tes from mosquitoes infected with P. falciparum. Malaria developed in all six control subjects, seven of eight subjects who received vaccine 1, and five of seven subjects who received vaccine 2. In contrast, on ly one of seven subjects who received vaccine 3 became infected (relat ive risk of infection, 0.14; 95 percent confidence interval, 0.02 to 0 .88; P<0.005). Conclusions A recombinant vaccine based on fusion of th e circumsporozoite protein and HBsAg plus a potent adjuvant can protec t against experimental challenge with P. falciparum sporozoites. After additional studies of protective immunity and the vaccination schedul e, field trials are indicated for this new vaccine against P. falcipar um malaria. (C) 1997, Massachusetts Medical Society.