Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization
Journal of Infectious Diseases
Albert Schweitzer Hospital, Medical Research Unit Lambaréné, Lambaréné, Gabon; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Kintampo Health Research Centre, Ghana Health Service, Kintampo, Ghana; London School of Hygiene and Tropical Medicine, London, United Kingdom; Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo District Hospital, Bagamoyo, Tanzania; GlaxoSmithKline Biologicals, Rixensart, Belgium; Program for Appropriate Technology in Health Malaria Vaccine Initiative, Bethesda, MD, United States; Swiss Tropical Institute, University of Basel, Basel, Switzerland
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 whole-cell 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). © 2010 by the Infectious Diseases Society of America. All rights reserved.
circumsporozoite protein; diphtheria antibody; diphtheria pertussis tetanus vaccine; Haemophilus influenzae type b vaccine; hepatitis B surface antibody; hepatitis B vaccine; hepb; immunoglobulin G antibody; immunological adjuvant; malaria vaccine; measles vaccine; oral poliomyelitis vaccine; protein antibody; protozoal protein; rts s as 01 e vaccine; stamaril; tetanus antibody; unclassified drug; yellow fever vaccine; diphtheria pertussis tetanus vaccine; Haemophilus influenzae type b polysaccharide vaccine; Haemophilus vaccine; hepatitis B vaccine; malaria vaccine; oral poliomyelitis vaccine; RTS,S AS01E vaccine; RTS,S-AS01E vaccine; alanine aminotransferase blood level; anemia; anorexia; antibody blood level; antibody response; article; bronchitis; clinical trial; conjunctivitis; controlled clinical trial; controlled study; coughing; diaper dermatitis; diarrhea; diphtheria; drowsiness; drug safety; drug screening; enteritis; enzyme linked immunosorbent assay; febrile convulsion; female; fever; Gabon; gastroenteritis; Ghana; Haemophilus infection; hepatitis B; human; immunization; immunogenicity; impetigo; infant; injection site induration; injection site pain; injection site swelling; irritability; major clinical study; malaria falciparum; male; measles; multicenter study; nonhuman; open study; otitis media; pertussis; phase 2 clinical trial; Plasmodium falciparum; pneumonia; priority journal; randomized controlled trial; rhinitis; rhinopharyngitis; rhinorrhea; seizure; sepsis; side effect; skin infection; staphylococcal skin infection; Tanzania; tetanus; upper respiratory tract infection; yellow fever; bacterial membrane; immunology; methodology; Bacterial Capsules; Diphtheria-Tetanus-Pertussis Vaccine; Female; Gabon; Ghana; Haemophilus Vaccines; Hepatitis B Vaccines; Humans; Immunization; Immunization, Secondary; Infant; Malaria Vaccines; Male; Poliovirus Vaccine, Oral; Tanzania