Evaluation of a malaria vaccine candidate comprised of full-length recombinant CSP formulated with SA-1 adjuvant, using RTS,S/AS01 as a benchmark

The world’s first malaria vaccine, RTS,S/AS01, is a recombinant VLP containing truncated CSP as the target antigen and formulated with a TLR4/QS21-containing adjuvant (AS01). In a large multi-center Phase 3 trial RTS,S/AS01 demonstrated a ~40% reduction in clinical malaria incidence in young African children, over ~4 years of follow-up, and is currently undergoing pilot implementation in 3 African countries. A next generation malaria vaccine with improved efficacy and durability offers the potential for even greater public health impact. A second generation of CSP-based malaria vaccine is expected to be superior to RTS,S/AS01 in protective efficacy and/or durability.

Activity 1. Evaluate antibody response durability in NHP model. Cynomolgus monkeys will be used as the primary animal model for immunogenicity because of their responsiveness to the TLR7 agonist in SA-1 and the similarity of induced functional antibody pharmacokinetics (PK) seen in humans. Monkeys will be immunized with of flCSP formulated with SA-1 or with AS01. 

Activity 2.1. Evaluate protective efficacy of antibodies induced by flCSP/AS01 and by RTS,S/AS01.  We will next compare the quality of the antibody response induced by flCSP or by RTS,S. Each immunogen will be tested in the same adjuvant, AS01, which is known to be active in mice. The experimental design will be closely based on our previously published qualification of in vivo models.

Activity 2.2. Evaluate protective efficacy induced by flCSP/SA-1.  To assure that the combination of flCSP with SA-1 adjuvant results in protective efficacy in the mouse model, we will conduct active immunization followed by challenge with sporozoites and measure protection from parasitemia.

At completion of T2020-252 we will conduct a Go/no go decision to recommend preclinical development of flCSP/SA-1. A go decision will require evidence of superior, durable protection.

GHIT - Grant detail

Product Development

Mar 2021 — Sep 2022

$999,733

Denmark
Japan
United States