advanced search

<< Back To Home

CSU 54/2008: ACCURACY OF REPORTED VACCINE COVERAGE / MALARIA VACCINE TRIALS

Sunday, 14th of December 2008

CSU 54/2008: ACCURACY OF REPORTED VACCINE COVERAGE / MALARIA VACCINE TRIALS

Previous Volume 359:2533-2544 December 11, 2008 Number 24 Next

Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants
Salim Abdulla, M.D., Ph.D., Rolf Oberholzer, M.D., Omar Juma, M.D., Sulende Kubhoja, M.D., M.M.E.D., Francisca Machera, A.M.O., Christopher Membi, A.D.M.L.S., Said Omari, D.M.L.T., Alwisa Urassa, B.P.A., Hassan Mshinda, Ph.D., Ajuza Jumanne, M.D., Nahya Salim, M.D., M.M.E.D., Mwanjaa Shomari, B.Sc., Thomas Aebi, M.D., David M. Schellenberg, M.D., Ph.D., Terrell Carter, M.H.S., Tonya Villafana, Ph.D., M.P.H., Marie-Ange Demoitié, M.Sc., Marie-Claude Dubois, M.Sc., Amanda Leach, M.R.C.P.C.H., Marc Lievens, M.Sc., Johan Vekemans, M.D., Ph.D., Joe Cohen, Ph.D., W. Ripley Ballou, M.D., and Marcel Tanner, Ph.D., M.P.H.

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.

 

Source Information

From the Bagamoyo Research and Training Centre of Ifakara Health Institute, Bagamoyo, Tanzania (S.A., R.O., O.J., F.M., C.M., S.O., A.U., H.M., A.J., N.S., M.S., T.A., D.M.S., M.T.); Swiss Tropical Institute, Basel, Switzerland (R.O., T.A., M.T.); Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania (S.K.); London School of Hygiene and Tropical Medicine, London (D.M.S.); Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative, Bethesda, MD (T.C., T.V.); GlaxoSmithKline Biologicals, Rixensart, Belgium (M.-A.D., M.-C.D., A.L., M.L., J.V., J.C.); and Bill and Melinda Gates Foundation, Seattle (W.R.B.).

This article (10.1056/NEJMoa0807773) was published at www.nejm.org on December 8, 2008.

Address reprint requests to Dr. Abdulla at the Bagamoyo Research and Training Centre, Ifakara Health Institute, Box 74, Bagamoyo Tanzania, or at sabdulla@ihi.or.tz .

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 coadministration 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 [ClinicalTrials.gov] .)