Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria

Abstract

Plasmodium vivax is responsible for the majority of malaria cases outside of Africa, and results in substantial morbidity. Transmission blocking vaccines are a potentially powerful component of a multi-faceted public health approach to controlling or eliminating malaria. We report the first phase 1 clinical trial of a P. vivax transmission blocking vaccine in humans. The Pvs25H vaccine is a recombinant protein derived from the Pvs25 surface antigen of P. vivax ookinetes. The protein was expressed in Saccharomyces cerevisiae, purified, and adsorbed onto Alhydrogel. Ten volunteers in each of three dose groups (5, 20, or 80 microg) were vaccinated by intramuscular injection in an open-label study at 0, 28 and 180 days. No vaccine-related serious adverse events were observed. The majority of adverse events causally related to vaccination were mild or moderate in severity. Injection site tenderness was the most commonly observed adverse event. Anti-Pvs25H antibody levels measured by ELISA peaked after the third vaccination. Vaccine-induced antibody is functionally active as evidenced by significant transmission blocking activity in the membrane feeding assay. Correlation between antibody concentration and degree of inhibition was observed. Pvs25H generates transmission blocking immunity in humans against P. vivax demonstrating the potential of this antigen as a component of a transmission blocking vaccine.

Fig. 1.

The anti-Pvs25H antibody units for the groups receiving 5 μg (short dashes), 20 μg (long dashes) or 80 μg (solid line) of Pvs25H/Alhydrogel^®.Geometric mean values for each group are shown at the sampling points with the standard error of the geometric mean. Arrows indicate the three vaccination days.

Fig. 2.

Individual (circles) and geometric mean (bars) anti-Pvs25H antibody units 2 weeks after volunteers received their second (open circles and open bars) and third (closed circles and hatched bars) vaccination with 5, 20 or 80 μg of Pvs25H/Alhydrogel^®.

Fig. 3.

Correlation of anti-Pvs25H antibody units with transmission blocking measured as a %reduction in oocysts per mosquito. The solid line and closed circles are membrane feeds using diluted sera. The dashed line and open circles are membrane feeds using undiluted sera. Lines are the non-linear regression fit of the data to a simple hyperbolic equation.