A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naive Adults.
Plasmodium falciparum
3-month challenge
RTS
S/AS01
controlled human malaria infection
delayed fractional dose
efficacy
immunogenicity
malaria
safety
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
13 10 2020
13 10 2020
Historique:
received:
23
03
2020
accepted:
17
07
2020
pubmed:
21
7
2020
medline:
12
3
2021
entrez:
21
7
2020
Statut:
ppublish
Résumé
A previous RTS,S/AS01B vaccine challenge trial demonstrated that a 3-dose (0-1-7-month) regimen with a fractional third dose can produce high vaccine efficacy (VE) in adults challenged 3 weeks after vaccination. This study explored the VE of different delayed fractional dose regimens of adult and pediatric RTS,S/AS01 formulations. A total of 130 participants were randomized into 5 groups. Four groups received 3 doses of RTS,S/AS01B or RTS,S/AS01E on a 0-1-7-month schedule, with the final 1 or 2 doses being fractional (one-fifth dose volume). One group received 1 full (month 0) and 1 fractional (month 7) dose of RTS,S/AS01E. Immunized and unvaccinated control participants underwent Plasmodium falciparum-infected mosquito challenge (controlled human malaria infection) 3 months after immunization, a timing chosen to potentially discriminate VEs between groups. The VE of 3-dose formulations ranged from 55% (95% confidence interval, 27%-72%) to 76% (48%-89%). Groups administered equivalent formulations of RTS,S/AS01E and RTS,S/AS01B demonstrated comparable VE. The 2-dose group demonstrated lower VE (29% [95% confidence interval, 6%-46%]). All regimens were well tolerated and immunogenic, with trends toward higher anti-circumsporozoite antibody titers in participants protected against infection. RTS,S/AS01E can provide VE comparable to an equivalent RTS,S/AS01B regimen in adults, suggesting a universal formulation may be considered. Results also suggest that the 2-dose regimen is inferior to the 3-dose regimens evaluated. NCT03162614.
Sections du résumé
BACKGROUND
A previous RTS,S/AS01B vaccine challenge trial demonstrated that a 3-dose (0-1-7-month) regimen with a fractional third dose can produce high vaccine efficacy (VE) in adults challenged 3 weeks after vaccination. This study explored the VE of different delayed fractional dose regimens of adult and pediatric RTS,S/AS01 formulations.
METHODS
A total of 130 participants were randomized into 5 groups. Four groups received 3 doses of RTS,S/AS01B or RTS,S/AS01E on a 0-1-7-month schedule, with the final 1 or 2 doses being fractional (one-fifth dose volume). One group received 1 full (month 0) and 1 fractional (month 7) dose of RTS,S/AS01E. Immunized and unvaccinated control participants underwent Plasmodium falciparum-infected mosquito challenge (controlled human malaria infection) 3 months after immunization, a timing chosen to potentially discriminate VEs between groups.
RESULTS
The VE of 3-dose formulations ranged from 55% (95% confidence interval, 27%-72%) to 76% (48%-89%). Groups administered equivalent formulations of RTS,S/AS01E and RTS,S/AS01B demonstrated comparable VE. The 2-dose group demonstrated lower VE (29% [95% confidence interval, 6%-46%]). All regimens were well tolerated and immunogenic, with trends toward higher anti-circumsporozoite antibody titers in participants protected against infection.
CONCLUSIONS
RTS,S/AS01E can provide VE comparable to an equivalent RTS,S/AS01B regimen in adults, suggesting a universal formulation may be considered. Results also suggest that the 2-dose regimen is inferior to the 3-dose regimens evaluated.
CLINICAL TRIAL REGISTRATION
NCT03162614.
Identifiants
pubmed: 32687161
pii: 5873826
doi: 10.1093/infdis/jiaa421
pmc: PMC7552430
doi:
Substances chimiques
Malaria Vaccines
0
Banques de données
ClinicalTrials.gov
['NCT03162614']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
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
1681-1691Investigateurs
Susan B Cicatelli
(SB)
Elizabeth H Duncan
(EH)
Kristin T Mills
(KT)
Christine E Lee
(CE)
Judith E Epstein
(JE)
Jessica J Cowden
(JJ)
Michele D Spring
(MD)
Melinda J Hamer
(MJ)
Nathanial K Copeland
(NK)
Viseth Ngauy
(V)
Donna M Tosh
(DM)
Justin M Curley
(JM)
Jason W Bennett
(JW)
Mark Riddle
(M)
Paige E Waterman
(PE)
Michael A Koren
(MA)
Jack N Hutter
(JN)
Elke Bergmann-Leitner
(E)
Jennifer Kooken
(J)
Evelina Angov
(E)
Kyle Peterson
(K)
Aurélia Leprince
(A)
Linda Murray
(L)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
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