A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.
BACKGROUND
The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion--based formulation (AS02) and a formulation based on liposomes (AS01).


RESULTS
In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01(E) or RTS,S/AS02(D), on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D)/AS01(E)) of 0.88 (95% CI: 0.68-1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.


CONCLUSIONS
RTS,S/AS01(E) proved similarly as well tolerated and immunogenic as RTS,S/AS02(D), completing an essential step in the age de-escalation process within the RTS,S clinical development plan.


BACKGROUND
ClinicalTrials.gov. NCT00307021.
Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
Bertrand
B
Lell
Selidji
S
Agnandji
Isabelle
I
von Glasenapp
Sonja
S
Haertle
Sunny
S
Oyakhiromen
Saadou
S
Issifou
Johan
J
Vekemans
Amanda
A
Leach
Marc
M
Lievens
Marie-Claude
MC
Dubois
Marie-Ange
MA
Demoitie
Terrell
T
Carter
Tonya
T
Villafana
W Ripley
WR
Ballou
Joe
J
Cohen
Peter G
PG
Kremsner
D000913:Antibodies, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005681:Gabon; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D016896:Treatment Outcome
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; C533816:RTS,S-AS01E vaccine; C533817:RTS,S-AS02D vaccine