By Sean Henahan, Access Excellence

WASHINGTON, D.C. (1/9/97) A novel anti-malaria vaccine could represent the most promising therapeutic approach to this mosquito-borne disease since the discovery of quinine, according to preliminary clinical studies conducted at the Walter Reed Army Institute of Research.

Graphic: Electron micrograph of a red blood cell containing the malaria parasite, Plasmodium falciparum.

The clinical study involved three groups of volunteers who received different formulations of an experimental vaccine, and a control group of nonvaccinated volunteers. The volunteers were challenged by way of infected-mosquito bites, with a strain of the malaria parasite (Plasmodium falciparum) known to be sensitive to antimalarial treatment.

Only marginal protection was seen in the first two study groups. But six of seven patients in a third group treated with an enhanced formulation remained free of infection. All of the nonvaccinated volunteers became infected.

The candidate vaccine is based on a recombinant circumsporozoite protein from the parasite which causes malaria. This is fused to hepatitis B surface antigen (HBsAg), unfused HBsAg and one of three adjuvant (a substance added to a vaccine to bolster the immune response) regimens. An adjuvant called QS-21 appeared to be the element that made the difference in the three treatment groups.

In an editorial accompanying the published study, Ruth Nussenzweig, M.D., Ph.D., of the New York University Medical Center commented that "The design of this trial, which used three formulations of the vaccine that differed only with respect to the adjuvants, showed the important role of these immune potentiators in inducing protection and high levels of antisporozoite antibodies. The striking effect of certain adjuvants on the efficacy of immunization is noteworthy and likely to be applicable to other microbial subunit vaccines."

This is the first time that an experimental vaccine has achieved a high degree of protection against the pre-erythrocytic stages of a human malaria parasite. The results of this study should allow a better understanding of the immunological requirements for the development of an efficacious malaria vaccine, after more than 20 years of research in this field.

The final development of a malaria vaccine suitable for broad application will still require considerable work. The parasite's surface protein that forms the basis of the current candidate vaccine is known to be highly variable in nature. In its current form, the candidate vaccine may not be effective against all variants. Duration of immunity and other parameters of the immune mechanisms involved also need to be understood.

In order to address these issues, a series of clinical trials, including a field trial of limited scope in West Africa, will be initiated in the course of the next few months with the existing vaccine. The possible need to incorporate additional antigens to the present vaccine will also be investigated.

The study appeared in The New England Journal of Medicine , January 9, 1997.