Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies

“…In all cases, the RH5.2-VLP was more immunogenic than the soluble protein ( Figures S3 A and S3B). A second experiment was performed using the same total dose of antigen to mirror clinical practice; here, given that a maximum dose of 50 μg of RH5.1 has been tested in adult humans 21 , 22 (with an assumed average body weight of ∼70 kg), we adjusted the dose to 16 ng for mice (average body weight of ∼22 g). Hence, a 16 ng total protein dose of the RH5.2-VLP was compared to a 16 ng dose of soluble RH5.2-ST or soluble RH5.1 (the current lead clinical antigen); all were formulated in Matrix-M adjuvant.…”

“…These vaccines have also induced serum immunoglobulin G (IgG) antibodies in humans that mediate functional growth inhibition activity (GIA) against P. falciparum in vitro . Notably, despite differences in the quantity of anti-RH5 serum IgG induced, the functional quality of the anti-RH5 human IgG is comparable, 19 , 22 i.e., these vaccines achieve the same amount of GIA in vitro per unit of anti-RH5 antibody, consistent with them all encoding immunogens based on RH5_FL. Importantly, GIA has also been shown to correlate with vaccine-induced efficacy against experimental P. falciparum blood-stage challenge of both Aotus monkeys 17 and UK adults, 21 with this mechanism of protection subsequently validated by passive transfer of anti-RH5 monoclonal antibody (mAb) in Aotus monkeys 23 and a humanized mouse model.…”

“… 17 These preclinical data supported the onward progression of RH5-based vaccine candidates to the clinic, with four early-phase clinical trials now completed in the UK or Tanzania; each of these studies utilized vaccines that deliver the full-length RH5 molecule (RH5_FL) using either a viral-vectored platform 18 , 19 or a recombinant protein called RH5.1 20 formulated in AS01 B adjuvant from GSK 21 or Matrix-M adjuvant from Novavax. 22 These vaccines have shown acceptable safety and reactogenicity profiles, with the highest levels of antibody observed when using the protein-in-adjuvant formulations 21 , 22 and/or when vaccinating Tanzanian infants or children as opposed to UK or Tanzanian adults. 19 , 22 The RH5.1/Matrix-M vaccine candidate has since progressed to a phase 2b field efficacy trial in 5- to 17-month-old children in Burkina Faso ( ClinicalTrials.gov NCT05790889 ).…”

“… 22 These vaccines have shown acceptable safety and reactogenicity profiles, with the highest levels of antibody observed when using the protein-in-adjuvant formulations 21 , 22 and/or when vaccinating Tanzanian infants or children as opposed to UK or Tanzanian adults. 19 , 22 The RH5.1/Matrix-M vaccine candidate has since progressed to a phase 2b field efficacy trial in 5- to 17-month-old children in Burkina Faso ( ClinicalTrials.gov NCT05790889 ).…”