A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

Selidji Todagbe Agnandji, Bertrand Lell, José Francisco Fernandes, Béatrice Peggy Abossolo, Barbara Gaelle Nfono Ondo Methogo, Anita Lumeka Kabwende, Ayola Akim Adegnika, Benjamin Mordmüller, Saadou Issifou, Peter Gottfried Kremsner, Jahit Sacarlal, Pedro Aide, Miguel Lanaspa, John J. Aponte, Sonia Machevo, Sozinho Acacio, Helder Bulo, Betuel Sigauque, Eusébio Macete, Pedro AlonsoSalim Abdulla, Nahya Salim, Rose Minja, Maxmillian Mpina, Saumu Ahmed, Ali Mohammed Ali, Ali Takadir Mtoro, Ali Said Hamad, Paul Mutani, Marcel Tanner, Halidou Tinto, Umberto D'Alessandro, Hermann Sorgho, Innocent Valea, Biébo Bihoun, Issa Guiraud, Berenger Kaboré, Olivier Sombié, Robert Tinga Guiguemdé, Jean Bosco Ouédraogo, Mary J. Hamel, Simon Kariuki, Martina Oneko, Chris Odero, Kephas Otieno, Norbert Awino, Meredith McMorrow, Vincent Muturi-Kioi, Kayla F. Laserson, Laurence Slutsker, Walter Otieno, Lucas Otieno, Nekoye Otsyula, Stacey Gondi, Allan Otieno, Victorine Owira, Esther Oguk, George Odongo, Jon Ben Woods, Bernhards Ogutu, Patricia Njuguna, Roma Chilengi, Pauline Akoo, Christine Kerubo, Charity Maingi, Trudie Lang, Ally Olotu, Philip Bejon, Kevin Marsh, Gabriel Mwambingu, Seth Owusu-Agyei, Kwaku Poku Asante, Kingsley Osei-Kwakye, Owusu Boahen, David Dosoo, Isaac Asante, George Adjei, Evans Kwara, Daniel Chandramohan, Brian Greenwood, John Lusingu, Samwel Gesase, Anangisye Malabeja, Omari Abdul, Coline Mahende, Edwin Liheluka, Lincoln Malle, Martha Lemnge, Thor G. Theander, Chris Drakeley, Daniel Ansong, Tsiri Agbenyega, Samuel Adjei, Harry Owusu Boateng, Theresa Rettig, John Bawa, Justice Sylverken, David Sambian, Anima Sarfo, Alex Agyekum, Francis Martinson, Irving Hoffman, Tisungane Mvalo, Portia Kamthunzi, Rutendo Nkomo, Tapiwa Tembo, Gerald Tegha, Mercy Tsidya, Jane Kilembe, Chimwemwe Chawinga, W. Ripley Ballou, Joe Cohen, Yolanda Guerra, Erik Jongert, Didier Lapierre, Amanda Leach, Marc Lievens, Opokua Ofori-Anyinam, Aurélie Olivier, Johan Vekemans, Terrell Carter, David Kaslow, Didier Leboulleux, Christian Loucq, Afiya Radford, Barbara Savarese, David Schellenberg, Marla Sillman, Preeti Vansadia, Sara Mian-McCarthy

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    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 personyear 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.)

    Original languageEnglish
    Pages (from-to)2284-2295
    Number of pages12
    JournalNew England Journal of Medicine
    Issue number24
    Publication statusPublished - 2012


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