NYVAC-PF7 - A POXVIRUS-VECTORED, MULTIANTIGEN, MULTISTAGE VACCINE CANDIDATE FOR PLASMODIUM-FALCIPARUM MALARIA

The highly attenuated NYVAC vaccinia virus strain has been utilized to develop a multiantigen, multistage vaccine candidate for malaria, a d isease that remains a serious global health problem and for which no h ighly effective vaccine exists. Genes encoding seven Plasmodium falcip arum antigens derived from the sporozoite (circumsporozoite protein an d sporozoite surface protein 2), liver (liver stage antigen 1), blood (merozoite surface protein 1, serine repeat antigen, and apical membra ne antigen 1), and sexual (25-kDa sexual-stage antigen) stages of the parasite life cycle were inserted into a single NYVAC genome to genera te NYVAC-P17. Each of the seven antigens was expressed in NYVAC-Pf7-in fected culture cells, and the genotypic and phenotypic stability of th e recombinant virus was demonstrated. When inoculated into rhesus monk eys, NYVAC-Pf7 was safe and well tolerated. Antibodies that recognize sporozoites, liver, blood, and sexual stages of P. falciparum were eli cited. Specific antibody responses against four of the P. falciparum a ntigens (circumsporozoite protein, sporozoite surface protein 2, meroz oite surface protein 1, and 25-kDa sexual-stage antigen) were characte rized. The results demonstrate that NYVAC-Pf7 is an appropriate candid ate vaccine for further evaluation in human clinical trials.