New paper published in Cell Reports Medicine

The Draper is group is happy to announce the publication of our new paper ‘Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies‘ in Cell Reports Medicine.

https://doi.org/10.1016/j.xcrm.2024.101654

In this paper Lloyd King et al. show that VAC063 clinical trial participants that were immunised with the RH5.1/AS01_Bvaccine candidate produced IgG antibodies that bind across the full-length of the RH5 molecule. Using in vitro assays of growth inhibition activity (GIA) we demonstrate that antibodies that bind the disordered regions of the RH5 molecule, such as the N-terminus, Intrinsic Loop and C-terminus, are non-growth inhibitory, whilst those targeting the structured diamond core are inhibitory.

Using this information, the RH5.1 immunogen was re-engineered by removing the disordered regions and stabilising the molecule by introducing 18 mutations, previously designed by our collaborator’s Dr Ivan Campeotto (when in Prof Higgins’ lab at Oxford) and Professor Sarel Fleishman (Weizmann Institute of Science in Israel) to enhance protein expression and stability. This re-engineered RH5 immunogen, renamed as “RH5.2” was then conjugated onto the surface of Hepatitis-B Virus-Like Particles (VLPs) using SpyTag:SpyCatcher technology. Vaccination of rodents with soluble RH5.2 or the RH5.2-VLP, both formulated in Matrix-M™ adjuvant (from Novavax), demonstrated that significantly more potent growth inhibitory antibodies were elicited compared to RH5.1/Matrix-M™. In addition, we show that in the same adjuvant the display of the RH5.2 immunogen on a VLP enables superior quantitative antibody immunogenicity with respect to soluble RH5.1 and RH5.2.

These preclinical studies are the first to identify a blood-stage malaria vaccine that significantly outperforms the current leading RH5 based blood-stage malaria candidate, RH5.1/Matrix-M™. The RH5.2-VLP/Matrix-M™ vaccine is now being tested in the BIO-001 Phase 1a trial in Oxford and the VAC086 Phase 1b clinical trial in The Gambia (NCT05978037 and NCT05357560) and we are eagerly awaiting results!