Assessment of safety, immnogenicity and efficacy of the PfRh5/matrix-M vaccine against blood-stage CHMI in Tanzania adults, and immunogenicity of PfRH5/ matrix-M vaccine in Tanzanian young children and infants

Objectives

This project proposes to develop a very promising four stage vaccine which will progress to a large phase IIb efficacy trial in West and East African 5-9 month olds. All four components of the vaccine have strong validation. The anti-sporozoite vaccine component, R21, is a next-generation RTS,S vaccine with a simpler but equally potent adjuvant matrix-M. This recently showed 82% sterile efficacy in UK phase II sporozoite challenge-trial using just 10 micrograms of R21 per dose (one-fifth of the standard RTS,S dose). The liver-stage vaccine employs adenoviral and MVA vectors that showed good safety and high efficacy in EDCTP-supported African trials and will now express conserved PfRH5 antigen that induces high-titer cross-strain neutralizing antibodies in phase I trials. The sexual-stage antigen is the conserved Pfs25, multimerized as a nanoparticle thereby enhancing antibody immunogenicity.

The research team will undertake a tightly coordinated series of lead in trials in 2018-2019 building towards a phase IIb efficacy trial in 5-9 month-olds in 2020-2022. They will first evaluate in East Africa the efficacy of the vaccine and its components in controlled human malaria infection trials, availing of this new capacity in Kenya and Tanzania.

In Tanzania, the research team will conduct a CHMI trial of the PfRH5/matrix-M malaria vaccine in Tanzanian adults, enrolling 60 subjects. The major hypothesis being addressed is that the PfRH5/matrix-M is safe and may induce protective immune responses in Tanzanian adults. The trial will take place at Bagamoyo, and will evaluate the safety, immunogenicity, and efficacy of the PfRH5/matrix-M vaccine against blood stage CHMI in Tanzanian adults.