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Background. The RTS,S/AS01E malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). Methods. This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01E when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01E at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and wholecell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01E at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. Results. The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01E coadministration groups. RTS,S/AS01E generated high anti-circumsporozoite protein and anti- hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01E at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. Conclusion. RTS,S/AS01E integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007. GlaxoSmithKline study ID number: 106369 (Malaria-050)

Background. The RTS,S/AS01E malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). Methods. This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01E when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01E at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and wholecell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01E at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. Results. The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01E coadministration groups. RTS,S/AS01E generated high anti-circumsporozoite protein and anti- hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01E at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. Conclusion. RTS,S/AS01E integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007. GlaxoSmithKline study ID number: 106369 (Malaria-050)