T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children

• Published in: PloS one Vol. 6; no. 4; p. e18891
• Main Authors: Ansong, Daniel, Asante, Kwaku P., Vekemans, Johan, Owusu, Sandra K., Owusu, Ruth, Brobby, Naana A. W., Dosoo, David, Osei-Akoto, Alex, Osei-Kwakye, Kingsley, Asafo-Adjei, Emmanuel, Boahen, Kwadwo O., Sylverken, Justice, Adjei, George, Sambian, David, Apanga, Stephen, Kayan, Kingsley, Janssens, Michel H., Lievens, Marc J. J., Olivier, Aurelie C., Jongert, Erik, Dubois, Patrice, Savarese, Barbara M., Cohen, Joe, Antwi, Sampson, Greenwood, Brian M., Evans, Jennifer A., Agbenyega, Tsiri, Moris, Philippe J., Owusu-Agyei, Seth
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 27.04.2011
• Subjects: Adults; Antigens; Biology; CD4 antigen; Children; Circumsporozoite protein; Drug dosages; Evaluation; Hepatitis; Hygiene; Immunization; Immunogenicity; Immunoglobulins; Interferon; Interleukin 2; Lymphocytes; Lymphocytes T; Malaria; Medical research; Medicine; Parasites; Pediatrics; Plasmodium falciparum; Rabies; Research facilities; Schedules; Science; T cell receptors; Teaching hospitals; Tumor necrosis factor-α; Vaccines; Vector-borne diseases; γ-Interferon; Ghana
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018891

Background The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01E or the oil-in-water based adjuvant AS02D induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults. Methods This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01E and RTS,S/AS02D in children aged 5–17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites. Results Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01E induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01E induced higher CD4 T cell responses as compared to RTS,S/AS02D when given on a 0,1,7-month schedule. Conclusions These findings support further Phase III evaluation of RTS,S/AS01E. The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation. Trial Registration ClinicalTrials.gov NCT00360230