A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants

Details

• Alternative Title:
  N Engl J Med
• Personal Author:
  Agnandji, Selidji Todagbe ; Lell, Bertrand ; Fernandes, José Francisco ; Abossolo, Béatrice Peggy ; Methogo, Barbara Gaelle Nfono Ondo ; Kabwende, Anita Lumeka ; Adegnika, Ayola Akim ; Mordmüller, Benjamin ; Issifou, Saadou ; Kremsner, Peter Gottfried ; Sacarlal, Jahit ; Aide, Pedro ; Lanaspa, Miguel ; Aponte, John J. ; Machevo, Sonia ; Acacio, Sozinho ; Bulo, Helder ; Sigauque, Betuel ; Macete, Eusébio ; Alonso, Pedro ; Abdulla, Salim ; Salim, Nahya ; Minja, Rose ; Mpina, Maxmillian ; Ahmed, Saumu ; Ali, Ali Mohammed ; Mtoro, Ali Takadir ; Hamad, Ali Said ; Mutani, Paul ; Tanner, Marcel ; Tinto, Halidou ; D'Alessandro, Umberto ; Sorgho, Hermann ; Valea, Innocent ; Bihoun, Biébo ; Guiraud, Issa ; Kaboré, Berenger ; Sombié, Olivier ; Guiguemdé, Robert Tinga ; Ouédraogo, Jean Bosco ; Hamel, Mary J. ; Kariuki, Simon ; Oneko, Martina ; Odero, Chris ; Otieno, Kephas ; Awino, Norbert ; McMorrow, Meredith ; Muturi-Kioi, Vincent ; Laserson, Kayla F. ; Slutsker, Laurence ; Otieno, Walter ; Otieno, Lucas ; Otsyula, Nekoye ; Gondi, Stacey ; Otieno, Allan ; Owira, Victorine ; Oguk, Esther ; Odongo, George ; Ben Woods, Jon ; Ogutu, Bernhards ; Njuguna, Patricia ; Chilengi, Roma ; Akoo, Pauline ; Kerubo, Christine ; Maingi, Charity ; Lang, Trudie ; Olotu, Ally ; Bejon, Philip ; Marsh, Kevin ; Owusu-Agyei, Seth ; Poku Asante, Kwaku ; Osei-Kwakye, Kingsley ; Boahen, Owusu ; Dosoo, David ; Asante, Isaac ; Adjei, George ; Kwara, Evans ; Chandramohan, Daniel ; Greenwood, Brian ; Lusingu, John ; Gesase, Samwel ; Malabeja, Anangisye ; Abdul, Omari ; Mahende, Coline ; Liheluka, Edwin ; Malle, Lincoln ; Lemnge, Martha ; Theander, Thor G. ; Drakeley, Chris ; Ansong, Daniel ; Agbenyega, Tsiri ; Adjei, Samuel ; Boateng, Harry Owusu ; Rettig, Theresa ; Bawa, John ; Sylverken, Justice ; Sambian, David ; Sarfo, Anima ; Agyekum, Alex ; Martinson, Francis ; Hoffman, Irving ; Mvalo, Tisungane ; Kamthunzi, Portia ; Nkomo, Rutendo ; Tembo, Tapiwa ; Tegha, Gerald ; Tsidya, Mercy ; Kilembe, Jane ; Chawinga, Chimwemwe ; Ballou, W. Ripley ; Cohen, Joe ; Guerra, Yolanda ; Jongert, Erik ; Lapierre, Didier ; Leach, Amanda ; Lievens, Marc ; Ofori-Anyinam, Opokua ; Olivier, Aurélie ; Vekemans, Johan ; Carter, Terrell ; Kaslow, David ; Leboulleux, Didier ; Loucq, Christian ; Radford, Afiya ; Savarese, Barbara ; Schellenberg, David ; Sillman, Marla ; Vansadia, Preeti
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• Corporate Authors:
  The RTS,S Clinical Trials Partnership ; Kintampo Health Research Center
• Description:
  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 Glaxo SmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.)
• Subjects:
  • Female
  • Humans
  • Immunization Schedule
  • Incidence
  • Infant
  • Malaria Vaccines
  • Malaria, Falciparum
  • Male
  • Plasmodium falciparum
  • Proportional Hazards Models
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• Source:
  N Engl J Med. 367(24):2284-2295
• Pubmed ID:
  23136909
• Pubmed Central ID:
  PMC10915853
• Document Type:
  Text
• Funding:
  092654/WT_/Wellcome TrustUnited Kingdom/ ; CC999999/ImCDC/Intramural CDC HHSUnited States/
• Genre:
  Journal Article
• Volume:
  367
• Issue:
  24
• Download URL:
  https://stacks.cdc.gov/view/cdc/151596/cdc_151596_DS1.pdf
• File Type:
  [PDF - 785.29 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:4419068a44aa8ff5552790c32554c8fdf1b6843e2912ea27cf61e5329c7e072b5c3b4c0fef2079c9aea52f1f3ac603e7749e08bebcfbf4cb59ae8b7950a4de82