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Title: Insights into long-lasting protection induced by RTS,S/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children
Author: Guinovart, Caterina
Aponte, John J.
Sacarlal, Jahit
Aide, Pedro Carlos Paulino
Leach, Amanda
Bassat Orellana, Quique
Macete, Eusébio
Dobaño, Carlota, 1969-
Lievens, Marc
Loucq, Christian
Ballou, W. Ripley
Cohen, Joe
Alonso, Pedro
Keywords: Vacuna de la malària
Assaigs clínics
Malaria vaccine
Clinical trials
Issue Date: 14-Apr-2009
Publisher: Public Library of Science (PLoS)
Abstract: Background: The pre-erythrocytic malaria vaccine RTS,S/AS02A has shown to confer protection against clinical malaria for at least 21 months in a trial in Mozambican children. Efficacy varied between different endpoints, such as parasitaemia or clinical malaria; however the underlying mechanisms that determine efficacy and its duration remain unknown. We performed a new, exploratory analysis to explore differences in the duration of protection among participants to better understand the protection afforded by RTS,S. Methodology/Principal Findings: The study was a Phase IIb double-blind, randomized controlled trial in 2022 children aged 1 to 4 years. The trial was designed with two cohorts to estimate vaccine efficacy against two different endpoints: clinical malaria (cohort 1) and infection (cohort 2). Participants were randomly allocated to receive three doses of RTS,S/AS02A or control vaccines. We did a retrospective, unplanned sub-analysis of cohort 2 data using information collected for safety through the health facility-based passive case detection system. Vaccine efficacy against clinical malaria was estimated over the first six-month surveillance period (double-blind phase) and over the following 12 months (single-blind phase), and analysis was per-protocol. Adjusted vaccine efficacy against first clinical malaria episodes in cohort 2 was of 35.4% (95% CI 4.5-56.3; p = 0.029) over the double-blind phase and of 9.0% (230.6-36.6; p = 0.609) during the single-blind phase. Conclusions/Significance: Contrary to observations in cohort 1, where efficacy against clinical malaria did not wane over time, in cohort 2 the efficacy decreases with time. We hypothesize that this reduced duration of protection is a result of the early diagnosis and treatment of infections in cohort 2 participants, preventing sufficient exposure to asexual-stage antigens. On the other hand, the long-term protection against clinical disease observed in cohort 1 may be a consequence of a prolonged exposure to low-dose blood-stage asexual parasitaemia.
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It is part of: PLoS One, 2009, vol. 4, num. 4, p. e5165
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)

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