Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial.
BACKGROUND
RTS,S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults. A previous report showed that this vaccine reduced risk of clinical malaria, delayed time to new infection, and reduced episodes of severe malaria over 6 months in African children. An important remaining issue is the durability of protection against clinical disease in these children.


METHODS
We did a randomised, controlled, phase IIb trial of RTS,S/AS02A given at 0, 1, and 2 months in 2022 Mozambican children aged 1-4 years. We previously determined vaccine efficacy (VE) against clinical malaria in a double-blind phase that included study months 2.5-8.5 (VE(2.5-8.5)). We now report VE in a single-blind phase up to month 21 (VE(8.5-21)). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature 37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) detected through a passive case detection system. We also determined VE for other case definitions and for episodes of severe malaria. This study is registered with the ClinicalTrials.gov identifier NCT00197041.


RESULTS
During the single-blind phase, VE(8.5-21) was 28.9% (95% CI 8.4-44.8; p=0.008). At month 21, prevalence of P falciparum infection was 29% lower in the RTS,S/AS02A group than in the control (p=0.017). Considering the entire study period, VE(2.5-21) was 35.3% (95% CI 21.6-46.6; p<0.0001) and VE(2.5-21) for severe malaria was 48.6% (95% CI 12.3-71.0; p=0.02).


CONCLUSIONS
These results show that RTS,S/AS02A confers partial protection in African children aged 1-4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months, and confirm the potential of malaria vaccines to become credible control tools for public-health use.
Alonso
Pedro L
PL
Centre de Salut Internacional, Hospital Clínic/ Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Villarroel 170, 08036 Barcelona, Spain. palonso@clinic.ub.es
Sacarlal
Jahit
J
Aponte
John J
JJ
Leach
Amanda
A
Macete
Eusebio
E
Aide
Pedro
P
Sigauque
Betuel
B
Milman
Jessica
J
Mandomando
Inacio
I
Bassat
Quique
Q
Guinovart
Caterina
C
Espasa
Mateu
M
Corachan
Sabine
S
Lievens
Marc
M
Navia
Margarita M
MM
Dubois
Marie-Claude
MC
Menendez
Clara
C
Dubovsky
Filip
F
Cohen
Joe
J
Thompson
Ricardo
R
Ballou
W Ripley
WR
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000145:classification / Q000276:immunology / Q000517:prevention & control*; D009073:Mozambique; D010963:Plasmodium falciparum / Q000276:immunology*; D012720:Severity of Illness Index; D016037:Single-Blind Method
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines