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

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 AS01(E) or the oil-in-water based adjuvant AS02(D) 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/AS01(E) and RTS, S/AS02(D) 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/AS01(E) induced CSP specific CD4 T cells producing IL-2, TNF-alpha, and IFN-gamma. 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/AS01(E) induced higher CD4 T cell responses as compared to RTS, S/AS02(D) when given on a 0,1,7-month schedule. Conclusions: These findings support further Phase III evaluation of RTS, S/AS01(E). The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation.