A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01(E) in a controlled human malaria infection challenge

Background: We previously demonstrated that RTS,S/AS01(B) and RTS,S/AS01(E) vaccination regimens including at least one delayed fractional dose can protect against Plasmodium falciparum malaria in a controlled human malaria infection (CHMI) model, and showed inferiority of a two-dose versus three-dose regimen. In this follow-on trial, we evaluated whether fractional booster vaccination extended or induced protection in previously protected (P-Fx) or non-protected (NP-Fx) participants. Methods: 49 participants (P-Fx: 25; NP-Fx: 24) received a fractional (1/5th dose-volume) RTS,S/AS01(E) booster 12 months post-primary regimen. They underwent P. falciparum CHMI three weeks later and were then followed for six months for safety and immunogenicity. Results: Overall vaccine efficacy against re-challenge was 53% (95% CI: 37-65%), and similar for P-Fx (52% [95% CI: 28-68%]) and NP-Fx (54% [95% CI: 29-70%]). Efficacy appeared unaffected by primary regimen or previous protection status. Anti-CS (repeat region) antibody geometric mean concentrations (GMCs) increased post-booster vaccination. GMCs were maintained over time in primary three-dose groups but declined in the two-dose group. Protection after re-challenge was associated with higher anti-CS antibody responses. The booster was well-tolerated. Conclusions: A fractional RTS,S/AS01(E) booster given one year after completion of a primary two- or threedose RTS,S/AS01 delayed fractional dose regimen can extend or induce protection against CHMI. (C) 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.