The purpose of this Phase 1/2 study, conducted in the United States, was to assess the safety, tolerability, and protective efficacy of a live attenuated Plasmodium falciparum sporozoite vaccine in malaria-naïve adults.
Subjects were randomized among four groups, with three groups receiving multiple subcutaneous or intradermal vaccinations of irradiated P. falciparum sporozoites from the Anopheles stephensi mosquito at one of three dose levels: 7,500 PfSPZ, 30,000 PfSPZ, or 135,000 PfSPZ. The fourth group received multiple subcutaneous or intradermal vaccinations at the 135,000 PfSPZ dose level only.
The study was designed with two objectives:
- Assess safety and tolerability of PfSPZ given subcutaneously or intradermally.
- Assess protective efficacy of PfSPZ given subcutaneously versus intradermally, against Plasmodium falciparum sporozoite challenge.
Outcomes/Next steps: Findings were published in Science in 2011.
A variety of local and systemic reactions were noted in subjects; however, these were found to be in line with reactogenicity experienced in previous studies.
Although PfSPZ was found to be safe, it was suboptimally immunogenic, and did not offer protective efficacy against Plasmodium falciparum sporozoite challenge.
Based on the outcomes of this study, the PATH Malaria Vaccine Initiative did not make any further investments.
Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, et al. Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity. Science. 2011;334(6055):475-480.