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 Lievens & 4 others Johan Vekemans, Joe Cohen, W. Ripley Ballou, Marcel Tanner

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    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. (ClinicalTrials.gov number, NCT00289185.)

    Original languageEnglish
    Pages (from-to)2533-2544
    Number of pages12
    JournalNew England Journal of Medicine
    Volume359
    Issue number24
    DOIs
    Publication statusPublished - 2008

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    Malaria Vaccines
    Safety
    Immunization Programs
    Haemophilus influenzae type b
    Hepatitis B Vaccines
    Confidence Intervals
    Malaria
    Haemophilus Vaccines
    Vaccines
    Immunization Schedule
    Diphtheria Toxoid
    Pertussis Vaccine
    Antigens
    Tetanus Toxoid
    Tanzania
    RTS,S-AS02D vaccine
    Antibodies
    Falciparum Malaria
    Plasmodium falciparum
    Hepatitis B Surface Antigens

    Cite this

    Abdulla, S., Oberholzer, R., Juma, O., Kubhoja, S., Machera, F., Membi, C., ... Tanner, M. (2008). Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. New England Journal of Medicine, 359(24), 2533-2544. https://doi.org/10.1056/NEJMoa0807773
    Abdulla, Salim ; Oberholzer, Rolf ; Juma, Omar ; Kubhoja, Sulende ; Machera, Francisca ; Membi, Christopher ; Omari, Said ; Urassa, Alwisa ; Mshinda, Hassan ; Jumanne, Ajuza ; Salim, Nahya ; Shomari, Mwanjaa ; Aebi, Thomas ; Schellenberg, David M. ; Carter, Terrell ; Villafana, Tonya ; Demoitié, Marie Ange ; Dubois, Marie Claude ; Leach, Amanda ; Lievens, Marc ; Vekemans, Johan ; Cohen, Joe ; Ballou, W. Ripley ; Tanner, Marcel. / Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. In: New England Journal of Medicine. 2008 ; Vol. 359, No. 24. pp. 2533-2544.
    @article{b418a76788fb4243b03924cf877ce89f,
    title = "Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants",
    abstract = "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. (ClinicalTrials.gov number, NCT00289185.)",
    author = "Salim Abdulla and Rolf Oberholzer and Omar Juma and Sulende Kubhoja and Francisca Machera and Christopher Membi and Said Omari and Alwisa Urassa and Hassan Mshinda and Ajuza Jumanne and Nahya Salim and Mwanjaa Shomari and Thomas Aebi and Schellenberg, {David M.} and Terrell Carter and Tonya Villafana and Demoiti{\'e}, {Marie Ange} and Dubois, {Marie Claude} and Amanda Leach and Marc Lievens and Johan Vekemans and Joe Cohen and Ballou, {W. Ripley} and Marcel Tanner",
    year = "2008",
    doi = "10.1056/NEJMoa0807773",
    language = "English",
    volume = "359",
    pages = "2533--2544",
    journal = "New England Journal of Medicine",
    issn = "0028-4793",
    publisher = "Massachusetts Medical Society",
    number = "24",

    }

    Abdulla, S, Oberholzer, R, Juma, O, Kubhoja, S, Machera, F, Membi, C, Omari, S, Urassa, A, Mshinda, H, Jumanne, A, Salim, N, Shomari, M, Aebi, T, Schellenberg, DM, Carter, T, Villafana, T, Demoitié, MA, Dubois, MC, Leach, A, Lievens, M, Vekemans, J, Cohen, J, Ballou, WR & Tanner, M 2008, 'Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants', New England Journal of Medicine, vol. 359, no. 24, pp. 2533-2544. https://doi.org/10.1056/NEJMoa0807773

    Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. / Abdulla, Salim; Oberholzer, Rolf; Juma, Omar; Kubhoja, Sulende; Machera, Francisca; Membi, Christopher; Omari, Said; Urassa, Alwisa; Mshinda, Hassan; Jumanne, Ajuza; Salim, Nahya; Shomari, Mwanjaa; Aebi, Thomas; Schellenberg, David M.; Carter, Terrell; Villafana, Tonya; Demoitié, Marie Ange; Dubois, Marie Claude; Leach, Amanda; Lievens, Marc; Vekemans, Johan; Cohen, Joe; Ballou, W. Ripley; Tanner, Marcel.

    In: New England Journal of Medicine, Vol. 359, No. 24, 2008, p. 2533-2544.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants

    AU - Abdulla, Salim

    AU - Oberholzer, Rolf

    AU - Juma, Omar

    AU - Kubhoja, Sulende

    AU - Machera, Francisca

    AU - Membi, Christopher

    AU - Omari, Said

    AU - Urassa, Alwisa

    AU - Mshinda, Hassan

    AU - Jumanne, Ajuza

    AU - Salim, Nahya

    AU - Shomari, Mwanjaa

    AU - Aebi, Thomas

    AU - Schellenberg, David M.

    AU - Carter, Terrell

    AU - Villafana, Tonya

    AU - Demoitié, Marie Ange

    AU - Dubois, Marie Claude

    AU - Leach, Amanda

    AU - Lievens, Marc

    AU - Vekemans, Johan

    AU - Cohen, Joe

    AU - Ballou, W. Ripley

    AU - Tanner, Marcel

    PY - 2008

    Y1 - 2008

    N2 - 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. (ClinicalTrials.gov number, NCT00289185.)

    AB - 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. (ClinicalTrials.gov number, NCT00289185.)

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    U2 - 10.1056/NEJMoa0807773

    DO - 10.1056/NEJMoa0807773

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    VL - 359

    SP - 2533

    EP - 2544

    JO - New England Journal of Medicine

    JF - New England Journal of Medicine

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    Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F, Membi C et al. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. New England Journal of Medicine. 2008;359(24):2533-2544. https://doi.org/10.1056/NEJMoa0807773