A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01

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

Journal

Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899

Informations de publication

Date de publication:
15 10 2021
Historique:
received: 17 05 2021
revised: 06 09 2021
accepted: 07 09 2021
pubmed: 2 10 2021
medline: 26 10 2021
entrez: 1 10 2021
Statut: ppublish

Résumé

We previously demonstrated that RTS,S/AS01 49 participants (P-Fx: 25; NP-Fx: 24) received a fractional (1/5th dose-volume) RTS,S/AS01 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. A fractional RTS,S/AS01 NCT03824236. linked to this article can be found on the Research Data as well as Figshare https://figshare.com/s/ee025150f9d1ac739361.

Sections du résumé

BACKGROUND
We previously demonstrated that RTS,S/AS01
METHODS
49 participants (P-Fx: 25; NP-Fx: 24) received a fractional (1/5th dose-volume) RTS,S/AS01
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
CLINICAL TRIAL REGISTRATION
NCT03824236. linked to this article can be found on the Research Data as well as Figshare https://figshare.com/s/ee025150f9d1ac739361.

Identifiants

pubmed: 34593270
pii: S0264-410X(21)01203-2
doi: 10.1016/j.vaccine.2021.09.024
pii:
doi:

Substances chimiques

Antibodies, Protozoan 0
Malaria Vaccines 0

Banques de données

ClinicalTrials.gov
['NCT03824236']

Types de publication

Clinical Trial, Phase II Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

6398-6406

Informations de copyright

Copyright © 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

James E Moon (JE)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: james.e.moon.mil@mail.mil.

Melissa E Greenleaf (ME)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: Melissa.e.greenleaf.ctr@mail.mil.

Jason A Regules (JA)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: jason.a.regules.mil@mail.mil.

Muriel Debois (M)

GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. Electronic address: muriel.l.debois@gsk.com.

Elizabeth H Duncan (EH)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: elizabeth.h.duncangooden.civ@mail.mil.

Martha Sedegah (M)

Naval Medical Research Center (NMRC), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: martha.sedegah.civ@mail.mil.

Ilin Chuang (I)

Naval Medical Research Center (NMRC), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: Ilin.chuang.mil@mail.mil.

Cynthia K Lee (CK)

PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. Electronic address: clee@path.org.

April K Sikaffy (AK)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: asikaffy@icongphs.com.

Lindsey S Garver (LS)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: lindsey.s.garverbaldwin.civ@mail.mil.

Karen Ivinson (K)

PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. Electronic address: kivinson@path.org.

Evelina Angov (E)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: evelina.angov.civ@mail.mil.

Danielle Morelle (D)

GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. Electronic address: danielle.morelle@gsk.com.

Marc Lievens (M)

GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. Electronic address: marc.lievens@gsk.com.

Christian F Ockenhouse (CF)

PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. Electronic address: cockenhouse@path.org.

Viseth Ngauy (V)

Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: viseth.ngauy.mil@mail.mil.

Opokua Ofori-Anyinam (O)

GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. Electronic address: opokua.ofori-anyinam@gsk.com.

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Classifications MeSH