Insights into long-lasting protection induced by RTS,S/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children.

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% (-30.6-36.6; 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00197041.

• Authors: Caterina Guinovart, John J Aponte, Jahit Sacarlal, Pedro Aide, Amanda Leach, Quique Bassat, Eusébio Macete, Carlota Dobaño, Marc Lievens, Christian Loucq, W Ripley Ballou, Joe Cohen, Pedro L Alonso
• Journal: PloS one (PLoS One) Vol. 4 Issue 4 Pg. e5165 ( 2009) ISSN: 1932-6203 [Electronic] United States
• PMID: 19365567 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Malaria Vaccines
• RTS,S-AS02A vaccine

Topics

• Adult
• Animals
• Child, Preschool
• Double-Blind Method
• Humans
• Infant
• Kaplan-Meier Estimate
• Malaria (prevention & control)
• Malaria Vaccines (therapeutic use)
• Mozambique
• Parasitemia (drug therapy)
• Treatment Outcome