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


RESULTS
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
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.


BACKGROUND
ClinicalTrials.gov NCT00197041.
Barcelona Centre for International Health Research, Hospital Clínic/IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Caterina
C
Guinovart
John J
JJ
Aponte
Jahit
J
Sacarlal
Pedro
P
Aide
Amanda
A
Leach
Quique
Q
Bassat
Eusébio
E
Macete
Carlota
C
Dobaño
Marc
M
Lievens
Christian
C
Loucq
W Ripley
WR
Ballou
Joe
J
Cohen
Pedro L
PL
Alonso
D000328:Adult; D000818:Animals; D002675:Child, Preschool; D004311:Double-Blind Method; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000627:therapeutic use*; D009073:Mozambique; D018512:Parasitemia / Q000188:drug therapy; D016896:Treatment Outcome
D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine