Abstract
BackgroundThe 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.MethodsThis 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.ResultsWhole 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.ConclusionsThese 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 RegistrationClinicalTrials.gov NCT00360230
Highlights
Malaria, caused by the protozoan parasite Plasmodium falciparum, affects millions of people annually
Implemented in the Expanded Program of Immunization (EPI), together with existing control measures such as wide spread use of insecticide treated nets, vector control and use of new generation anti-malaria drugs, RTS,S may contribute to sustained malaria control
Combination of this fusion protein with native hepatitis B surface antigen results in the spontaneous formation of RTS,S virus-like particles [1]. This antigen formulated with the AS02 adjuvant induces CSP specific adaptive immune responses and protection against infection in controlled parasite challenge studies [2,3,4,5] as well in semi-immune adults, children and infants living in malaria-endemic regions [6,7,8,9,10,11]
Summary
Malaria, caused by the protozoan parasite Plasmodium falciparum, affects millions of people annually. A new RTS,S formulation containing the AS01 adjuvant and consisting of MPL, QS21 and liposomes was recently selected as an alternative to RTS,S/AS02 on the basis of its ability to induce comparable, or better, CSP-specific antibody responses and greater T cell responses in small animal models and non-human primates than did AS02 [12,13] This effect was confirmed in a Phase IIa controlled parasite challenge study performed in malaria naıve adults at the Walter Reed Army Institute of Research where, compared to RTS,S/AS02, RTS,S/AS01 was shown to be well tolerated, to induce strong humoral and cellular immune responses, and to improve protection against P. falciparum challenge [5]. 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
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