Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial.
BACKGROUND
Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess vaccine efficacy, immunogenicity, and safety in young African children.


METHODS
We did a double-blind, phase IIb, randomised controlled trial in Mozambique in 2022 children aged 1-4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature > or =37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417). Analysis was per protocol.


RESULTS
115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per-protocol analysis. Vaccine efficacy for the first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37% lower in the RTS,S/AS02A group compared with the control group (11.9% vs 18.9%; p=0.0003). Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In cohort 2, vaccine efficacy for extending time to first infection was 45.0% (31.4-55.9; p<0.0001).


CONCLUSIONS
The RTS,S/AS02A vaccine was safe, well tolerated, and immunogenic. Our results show development of an effective vaccine against malaria is feasible.
Centre de Salut Internacional, Hospital Clínic/IDIBAPS, Universitat de Barcelona, Barcelona, Spain. palonso@clinic.ub.es
Pedro L
PL
Alonso
Jahit
J
Sacarlal
John J
JJ
Aponte
Amanda
A
Leach
Eusebio
E
Macete
Jessica
J
Milman
Inacio
I
Mandomando
Bart
B
Spiessens
Caterina
C
Guinovart
Mateu
M
Espasa
Quique
Q
Bassat
Pedro
P
Aide
Opokua
O
Ofori-Anyinam
Margarita M
MM
Navia
Sabine
S
Corachan
Marc
M
Ceuppens
Marie-Claude
MC
Dubois
Marie-Ange
MA
Demoitié
Filip
F
Dubovsky
Clara
C
Menéndez
Nadia
N
Tornieporth
W Ripley
WR
Ballou
Ricardo
R
Thompson
Joe
J
Cohen
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002675:Child, Preschool; D004311:Double-Blind Method; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000469:parasitology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology; D034101:Sporozoites / Q000276:immunology; D016896:Treatment Outcome
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine