Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization.

Abstract

BACKGROUND:

The RTS,S/AS01(E) 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/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) 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/AS01(E) 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/AS01(E) coadministration groups. RTS,S/AS01(E) 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/AS01(E) 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/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).

• Authors: Selidji T Agnandji, Kwaku Poku Asante, John Lyimo, Johan Vekemans, Solange S Soulanoudjingar, Ruth Owusu, Mwanajaa Shomari, Amanda Leach, Jose Fernandes, David Dosoo, Maria Chikawe, Saadou Issifou, Kingsley Osei-Kwakye, Marc Lievens, Maria Paricek, Stephen Apanga, Grace Mwangoka, Blaise Okissi, Evans Kwara, Rose Minja, Jorn Lange, Owusu Boahen, Kingsley Kayan, George Adjei, Daniel Chandramohan, Erik Jongert, Marie-Ange Demoitié, Marie-Claude Dubois, Terrel Carter, Preeti Vansadia, Tonya Villafana, Marla Sillman, Barbara Savarese, Didier Lapierre, William Ripley Ballou, Brian Greenwood, Marcel Tanner, Joe Cohen, Peter G Kremsner, Bertrand Lell, Seth Owusu-Agyei, Salim Abdulla
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 202 Issue 7 Pg. 1076-87 (Oct 01 2010) ISSN: 1537-6613 [Electronic] United States
• PMID: 20735271 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Diphtheria-Tetanus-Pertussis Vaccine
• Haemophilus Vaccines
• Haemophilus influenzae type b polysaccharide vaccine
• Hepatitis B Vaccines
• Malaria Vaccines
• Poliovirus Vaccine, Oral
• RTS,S-AS01E vaccine

Topics

• Bacterial Capsules (administration & dosage, adverse effects, immunology)
• Diphtheria-Tetanus-Pertussis Vaccine (administration & dosage, adverse effects, immunology)
• Female
• Gabon
• Ghana
• Haemophilus Vaccines (administration & dosage, adverse effects, immunology)
• Hepatitis B Vaccines (administration & dosage, adverse effects, immunology)
• Humans
• Immunization (methods)
• Immunization, Secondary (methods)
• Infant
• Malaria Vaccines (administration & dosage, adverse effects, immunology)
• Male
• Poliovirus Vaccine, Oral (administration & dosage, adverse effects, immunology)
• Tanzania