Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area.
BACKGROUND
This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.


METHODS
A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1ratio1ratio1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.


RESULTS
Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: -15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: -11.6 to 58.2, p = 0.128).


CONCLUSIONS
Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.


BACKGROUND
Clinicaltrials.gov NCT00197054.
Polhemus
Mark E
ME
US Army Medical Research Unit-Kenya, Nairobi, Kenya. mark.polhemus@us.army.mil
Remich
Shon A
SA
Ogutu
Bernhards R
BR
Waitumbi
John N
JN
Otieno
Lucas
L
Apollo
Stella
S
Cummings
James F
JF
Kester
Kent E
KE
Ockenhouse
Christian F
CF
Stewart
Ann
A
Ofori-Anyinam
Opokua
O
Ramboer
Isabelle
I
Cahill
Conor P
CP
Lievens
Marc
M
Dubois
Marie-Claude
MC
Demoitie
Marie-Ange
MA
Leach
Amanda
A
Cohen
Joe
J
Ballou
W Ripley
WR
Heppner
D Gray
DG
D000328:Adult; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method; D016896:Treatment Outcome
D017780:Malaria Vaccines