MICA: Large-scale vaccine fill and Phase I clinical trial of the RH5.1/Matrix-M vaccine against blood-stage Plasmodium falciparum malaria

Delivery approaches and platforms that can impart sustained and durable immunity are essential to the success of vaccines against a wide variety of difficult human diseases. Examples include seasonal respiratory viruses (such as influenza, RSV), emerging/pandemic pathogens (such as SARS-CoV-2) as well as parasites (such as Plasmodium – the causative agent of malaria).
The first vaccine to show in vivo impact in humans against the disease-causing blood-stage form of the P. falciparum human malaria parasite was developed previously. The vaccine (called RH5.1) targets the conserved and essential RH5 antigen used by the parasite to invade erythrocytes. With previous MRC DPFS funding support this novel recombinant protein was successfully produced to high yield using new platform biomanufacturing technologies, and with USAID funding, RH5.1 formulated in AS01 adjuvant from GSK was tested in a large Phase I/IIa trial in healthy UK adults. A “delayed-fractional booster” immunisation regimen was identified that dramatically improved the maintenance of the human antibody response over 2.5 years’ follow-up, as compared to routine vaccine boosting at monthly intervals. Now the proposal sets to fill the remaining RH5.1 vaccine material (~250mg) to give a second vaccine batch. RH5.1/Matrix-M offers the possibility of an efficacious blood-stage malaria vaccine that can proceed to future field efficacy testing, as well as a route to identification of a delayed-booster immunisation regimen that affords long-lasting human immunity. Importantly, this work will also exemplify robust vaccine platform delivery technologies that have broad applicability to a range of human diseases.

Project details

Vaccines (Immune Correlates)

Aug 2021 — Aug 2024

$2.55M

Sweden
United Kingdom