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
James E Moon, Melissa E Greenleaf, Jason A Regules, Muriel Debois, Elizabeth H Duncan, Martha Sedegah, Ilin Chuang, Cynthia K Lee, April K Sikaffy, Lindsey S Garver, Karen Ivinson, Evelina Angov, Danielle Morelle, Marc Lievens, Christian F Ockenhouse, Viseth Ngauy, Opokua Ofori-Anyinam, RTS S Malaria Vaccine Working Group, James E Moon, Melissa E Greenleaf, Jason A Regules, Muriel Debois, Elizabeth H Duncan, Martha Sedegah, Ilin Chuang, Cynthia K Lee, April K Sikaffy, Lindsey S Garver, Karen Ivinson, Evelina Angov, Danielle Morelle, Marc Lievens, Christian F Ockenhouse, Viseth Ngauy, Opokua Ofori-Anyinam, RTS S Malaria Vaccine Working Group
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.
Keywords: Booster; Controlled human malaria infection re-challenge; Efficacy; Fractional dose; Plasmodium falciparum malaria; RTS; S/AS01.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lievens, Marc; Morelle, Danielle; Debois, Muriel and Ofori-Anyinam, Opokua; are employees of the GSK group of companies. Debois, Muriel; Morelle, Danielle; Lievens, Marc; Ofori-Anyinam, Opokua have restricted shares in the GSK group of companies. Greenleaf, Melissa; Duncan, Elizabeth; Chuang, Ilin; Angov, Evelina; Ivinson, Karen; Komisar, Jack; Lee, Cynthia; Moon, James; Ockenhouse, Christian; Regules, Jason; Garver, Lindsey; Sedegah, Martha; Sikaffy, April K; Ngauy, Viseth declare no competing interests.
Copyright © 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed