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; Johan Vekemans; Joe Cohen; W. Ripley Ballou; Marcel Tanner

doi:10.1056/NEJMoa0807773

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 journal › Article › peer-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 language	English
Pages (from-to)	2533-2544
Number of pages	12
Journal	New England Journal of Medicine
Volume	359
Issue number	24
DOIs	https://doi.org/10.1056/NEJMoa0807773
Publication status	Published - 2008

Access to Document

10.1056/NEJMoa0807773

Cite this

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, D. M., Carter, T., Villafana, T., Demoitié, M. A., Dubois, M. C., Leach, A., ... 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

@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

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.)

UR - http://www.scopus.com/inward/record.url?scp=57649123026&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa0807773

DO - 10.1056/NEJMoa0807773

M3 - Article

VL - 359

SP - 2533

EP - 2544

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 24

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this