PHASE I IIA SAFETY, IMMUNOGENICITY, AND EFFICACY TRIAL OF NYVAC-PF7, A POX-VECTORED, MULTIANTIGEN, MULTISTAGE VACCINE CANDIDATE FOR PLASMODIUM-FALCIPARUM MALARIA/

Candidate malaria vaccines have failed to elicit consistently protecti ve immune responses against challenge with Plasmodium falciparum. NYVA C-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes i nserted into its genome, was tested in a phase I/IIa safety, immunogen icity, and efficacy vaccine trial in human volunteers. Malaria genes i nserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerate d but variably immunogenic. While antibody responses were generally po or, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infe cted Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunt eers who received either the low or high dose of vaccine compared with control volunteers.