Rts SClinical Trials Partnership
Agnandji ST
Lell B
Fernandes JF
Abossolo BP
Methogo BG
Kabwende AL
Adegnika AA
Mordmuller B
Issifou S
Kremsner PG
Sacarlal J
Aide P
Lanaspa M
Aponte JJ
Machevo S
Acacio S
Bulo H
Sigauque B
Macete E
Alonso P
Abdulla S
Salim N
Minja R
Mpina M
Ahmed S
Ali AM
Mtoro AT
Hamad AS
Mutani P
Tanner M
Tinto H
D'Alessandro U
Sorgho H
Valea I
Bihoun B
Guiraud I
Kabore B
Sombie O
Guiguemde RT
Ouedraogo JB
Hamel MJ
Kariuki S
Oneko M
Odero C
Otieno K
Awino N
McMorrow M
Muturi-Kioi V
Laserson KF
Slutsker L
Otieno W
Otieno L
Otsyula N
Gondi S
Otieno A
Owira V
Oguk E
Odongo G
Woods JB
Ogutu B
Njuguna P
Chilengi R
Akoo P
Kerubo C
Maingi C
Lang T
Olotu A
Bejon P
Marsh K
Mwambingu G
Owusu-Agyei S
Asante KP
Osei-Kwakye K
Boahen O
Dosoo D
Asante I
Adjei G
Kwara E
Chandramohan D
Greenwood B
Lusingu J
Gesase S
Malabeja A
Abdul O
Mahende C
Liheluka E
Malle L
Lemnge M
Theander TG
Drakeley C
Ansong D
Agbenyega T
Adjei S
Boateng HO
Rettig T
Bawa J
Sylverken J
Sambian D
Sarfo A
Agyekum A
Martinson F
Hoffman I
Mvalo T
Kamthunzi P
Nkomo R
Tembo T
Tegha G
Tsidya M
Kilembe J
Chawinga C
Ballou WR
Cohen J
Guerra Y
Jongert E
Lapierre D
Leach A
Lievens M
Ofori-Anyinam O
Olivier A
Vekemans J
Carter T
Kaslow D
Leboulleux D
Loucq C
Radford A
Savarese B
Schellenberg D
Sillman M
Vansadia P
N Engl J Med. 2012;3672284-95
BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).
