Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants

Salim Abdulla, Rolf Oberholzer, Omar Juma, Sulende Kubhoja, Francisca Machera, Christopher Membi, Said Omari, Alwisa Urassa, Hassan Mshinda, Ajuza Jumanne, Nahya Salim, Mwanjaa Shomari, Thomas Aebi, David M. Schellenberg, Terrell Carter, Tonya Villafana, Marie Ange Demoitié, Marie Claude Dubois, Amanda Leach, Marc LievensJohan Vekemans, Joe Cohen, W. Ripley Ballou, Marcel Tanner

    Research output: Contribution to journalArticlepeer-review


    BACKGROUND: The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants. METHODS: In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with co-administration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives. RESULTS: At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P = 0.01). CONCLUSIONS: The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. ( number, NCT00289185.)

    Original languageEnglish
    Pages (from-to)2533-2544
    Number of pages12
    JournalNew England Journal of Medicine
    Issue number24
    Publication statusPublished - 2008


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