Phase I trial of the SPf66 malaria vaccine in a malaria-experienced population in Southeast Asia.
ABSTRACT In preparation for a recently reported, independent field trial of SPf66 malaria vaccine efficacy in Thailand, we first established the safety and immunogenicity of two clinical lots of U.S. manufactured lots of SPf66 in a series of overlapping Phase I studies. The vaccine was produced in approved laboratories using good manufacturing practices. Two clinical lots of alum-adsorbed SPf66 were evaluated in a combined, open-label, Phase I clinical trial involving 50 healthy, malaria-experienced Karen adults and children. Volunteers were grouped by age and immunized sequentially. Group 1 had 30 adults. Group 2 had 10 children 8-15 years of age, and Group 3 had 10 children 2-6 years of age. The SPf66 vaccine was well tolerated in this malaria-experienced population. The most common side effects were erythema, induration, warmth, and tenderness at the site of injection, which typically resolved within 24-48 hr. One adult volunteer developed an acute urticarial rash following the third dose. Among adults, and to a lesser extent older children females had more local reactions than their male counterparts. Seroconversion to SPf66 by enzyme-linked immunosorbent assay occurred in 76% of volunteers receiving two or three doses. This vaccine was safe and immunogenic in malaria-experienced Karen adults and children. This study establishes the comparability of U.S.-manufactured SPf66 with that of Colombian origin, and is important for interpreting the efficacy results of U.S.-manufactured SPf66 in the same study population.