Study of Controlled Human Malaria Infections to Evaluate Protection After Intravenous or Intramuscular Administration of PfSPZ Vaccine in Malaria-Naive Adults

Objectives

The Plasmodium falciparum sporozoites (PfSPZ) vaccine administered at 1.35 times 10(5) PfSPZ per injection by the IV route on a schedule of 5 vaccinations was previously shown to confer protection in all vaccinated subjects against CHMI performed shortly after last vaccination. However, there was limited durability of protection in a small number of protected subjects who were rechallenged several months later.

This study is designed to substantiate the initial results with the IV vaccination route for protection against CHMI. Based on the potential importance of dose and schedule in optimizing sustained immunity with this vaccine, an increase in PfSPZ IV dosage on schedules of 3 to 5 vaccinations will be evaluated for protection against CHMI conducted early (about 3 weeks) and late (about 24 weeks) after completion of vaccinations. To assess if a higher dose given by another route confers protection, one group will receive PfSPZ IM, with half of the amount administered in each arm on a schedule with 4 vaccination.

The primary objectives of the study are related to the safety and tolerability of vaccinations by the IV and IM routes of administration and protection against Plasmodium falciparum (Pf) challenge performed via a well-established CHMI procedure early (2-4 weeks) after completing schedules of 3 to 5 vaccinations. The secondary objective is related to the durability of protection at 20-26 weeks after the last vaccination and exploratory objectives are related to the immunogenicity of the PfSPZ Vaccine and identifying potential immune correlates of protection