SAFETY, IMMUNOGENICITY, AND PILOT EFFICACY OF PLASMODIUM-FALCIPARUM SPOROZOITE AND ASEXUAL BLOOD-STAGE COMBINATION VACCINE IN SWISS ADULTS

This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and cli nical malaria caused by asexual blood stages. In a phase 1 study of sa fety and immunogenicity, two recombinant proteins (Ro 36-2717, a circu msporozoite [CS] protein) construct with a molecular mass of 35 kD, an d Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a mol ecular mass of 25 kD) adsorbed onto alum were injected in two low (20 mu g) or two high (100 mu g) doses in the right and left deltoid muscl es of 33 healthy Swiss volunteers; six other volunteers received a pla cebo (alum alone). Twenty six participants reported 51 immunization-re lated adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assa y peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, wi th the increase in MSA-2 titer being weaker than that for the CS prote in. After a third immunization, five vaccinees volunteered to be chall enged by three or four infective bites of Anopheles stephensi. Prepate nt and incubation periods in all five were comparable with unvaccinate d historic controls challenged under similar conditions, and all had s ymptoms of clinical falciparum malaria. We conclude that the vaccine c omponents were safe and immunogenic but there was no evidence that thi s immunization regimen with the CS protein plus MSA-2 component was ab le to prevent infection. Because the protocol required treatment in le ss than or equal to 24 hr after detection of parasitemia, the contribu tion of MSA-2 as an anti-disease vaccine candidate will be further eva luated in a field trial.