Antisporozoite Vaccine for Malaria: Experimental Basis and Current Status

Abstract

A major sporozoite surface antigen, the circumsporozoite protein, has been identified in all four malaria parasites affecting humans and in numerous species causing malaria in rodents and simians. The corresponding genes have been cloned and sequenced, and considerable similarities are apparent. An extensive central region of these proteins consists of tandemly repeated sequences of four to 16 amino acids. The sporozoite protein of Plasmodium falciparum has 37–41 repeats of four amino acids: NANP (asparagines-alanine-asparagine-proline). Most sera from people in endemic areas that react with sporozoites also recognize the dodecamer (NANP)₃. Conjugated to a carrier, (NANP)₃ is an excellent immunogen for rabbits and mice. NANP has recently served as the basis for two experimental malaria vaccines tested in volunteers. One of these vaccines, (NANP)₃₂ tet₃₂, was genetically engineered in Escherichia coli; the other consisted of the synthetic peptide (NANP)₃ conjugated to tetanus toxoid. Most peptide-immunized volunteers developed antipeptide/sporozoite antibodies; however, there was no booster effect, and only one of three individuals was completely protected. For optimal protection, future vaccines must not only contain the B cell epitope but also induce T helper cells and cytotoxic T cells producing interferon-γ, which has been shown to inhibit the development of liver-stage parasites.