Title:
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Insights into long-lasting protection induced by RTS,S/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children
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Author:
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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
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Other authors:
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Universitat de Barcelona |
Abstract:
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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. |
Subject(s):
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-Vacuna de la malària -Infants -Moçambic -Assaigs clínics -Malaria vaccine -Children -Mozambique -Clinical trials |
Rights:
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cc-by (c) Guinovart, C. et al., 2009
http://creativecommons.org/licenses/by/3.0/es |
Document type:
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Article Article - Published version |
Published by:
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Public Library of Science (PLoS)
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