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
• 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:
  Africa Female Humans Immunization Schedule Incidence Infant Intention To Treat Analysis Malaria, Falciparum Malaria Vaccines Male Plasmodium Falciparum Proportional Hazards Models Treatment Outcome Vaccines, Synthetic

  More +
• Source:
  N Engl J Med. 367(24):2284-2295
• Pubmed ID:
  23136909
• Pubmed Central ID:
  PMC10915853
• Document Type:
  Journal Article
• Funding:
  092654/WT_/Wellcome TrustUnited Kingdom/ ; CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  367
• Issue:
  24
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:3e737d9c42ef9d7e1e0e6f229b47ab1e9623a6bcb99559323e75f749f1ff7617
• Download URL:
  https://stacks.cdc.gov/view/cdc/151596/cdc_151596_DS1.pdf
• File Type:
  [PDF - 785.29 KB ]