A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01E in a controlled human malaria infection challenge

for the RTS S Malaria Vaccine Working Group

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: We previously demonstrated that RTS,S/AS01B and RTS,S/AS01E 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/AS01E 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/AS01E booster given one year after completion of a primary two- or three-dose RTS,S/AS01 delayed fractional dose regimen can extend or induce protection against CHMI. Clinical Trial Registration: NCT03824236. linked to this article can be found on the Research Data as well as Figshare https://figshare.com/s/ee025150f9d1ac739361

Original languageEnglish
Pages (from-to)6398-6406
Number of pages9
JournalVaccine
Volume39
Issue number43
DOIs
StatePublished - 15 Oct 2021
Externally publishedYes

Keywords

  • Booster
  • Controlled human malaria infection re-challenge
  • Efficacy
  • Fractional dose
  • Plasmodium falciparum malaria
  • RTS
  • S/AS01

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