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.
Lell
Bertrand
B
Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
Agnandji
Selidji
S
von Glasenapp
Isabelle
I
Haertle
Sonja
S
Oyakhiromen
Sunny
S
Issifou
Saadou
S
Vekemans
Johan
J
Leach
Amanda
A
Lievens
Marc
M
Dubois
Marie-Claude
MC
Demoitie
Marie-Ange
MA
Carter
Terrell
T
Villafana
Tonya
T
Ballou
W Ripley
WR
Cohen
Joe
J
Kremsner
Peter G
PG
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