T cell responses to the RTS,S/AS01(E) and RTS,S/AS02(D) malaria candidate vaccines administered according to different schedules to Ghanaian children

Background

The Plasmodium falciparum pre-erythrocytic stage candidatevaccine RTS,S is being developed for protection of young children againstmalaria in sub-Saharan Africa. RTS,S formulated with the liposome basedadjuvant AS01_E or the oil-in-water based adjuvantAS02_D induces P. falciparum circumsporozoite(CSP) antigen-specific antibody and T cell responses which have beenassociated with protection in the experimental malaria challenge model inadults.

Methods

This study was designed to evaluate the safety and immunogenicity inducedover a 19 month period by three vaccination schedules (0,1-, 0,1,2- and0,1,7-month) of RTS,S/AS01_E and RTS,S/AS02_D inchildren aged 5–17 months in two research centers in Ghana. ControlRabies vaccine using the 0,1,2-month schedule was used in one of two studysites.

Results

Whole blood antigen stimulation followed by intra-cellular cytokine stainingshowed RTS,S/AS01_E induced CSP specific CD4 T cells producingIL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-monthschedule. RTS,S/AS01_E induced higher CD4 T cell responses ascompared to RTS,S/AS02_D when given on a 0,1,7-month schedule.

Conclusions

These findings support further Phase III evaluation ofRTS,S/AS01_E. The role of immune effectors and immunizationschedules on vaccine protection are currently under evaluation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00360230","term_id":"NCT00360230"}}NCT00360230