Phase I/IIa Clinical Trial of RH5.1/AS01B Vaccine for Blood-Stage Malaria Shows Promising Safety and Immunogenicity

The VAC063 study was designed to assess the safety, immunogenicity, and efficacy of the RH5.1/AS01B vaccine, a recombinant blood-stage malaria protein formulated with GSK’s adjuvant system AS01B. The RH5.1 protein, based on the PfRH5 antigen from the 3D7 clone of P. falciparum, was produced using a stable Drosophila melanogaster Schneider 2 (S2) cell line. The vaccine was manufactured under Good Manufacturing Practice (GMP) and stored at ultra-low temperatures before use.

The trial was conducted in the UK across multiple centers, enrolling 88 healthy, malaria-naive adults aged 18 to 45. Participants received the vaccine in doses of 2 µg, 10 µg, and 50 µg, with the primary objectives being to assess the vaccine's safety, its in vitro growth inhibition activity (GIA) against P. falciparum parasites, and its efficacy in reducing the parasite multiplication rate (PMR) in a blood-stage controlled human malaria infection (CHMI) model.

Secondary objectives included evaluating the vaccine's immunogenicity and the durability of any reduction in PMR after a secondary blood-stage CHMI. The study also implemented strict safety monitoring and stopping rules to ensure participant safety, particularly given the first-in-human nature of the dose escalation study.

Results indicated that the RH5.1/AS01B vaccine was generally safe and well-tolerated, with most adverse events being mild to moderate in severity. The vaccine demonstrated potential efficacy in reducing the PMR, suggesting a promising avenue for malaria vaccine development. The study's findings contribute valuable insights into the safety and immunogenicity of the RH5.1/AS01B vaccine, paving the way for further research and development in malaria prevention strategies.