circumsporozoite-specific t cell responses in children vaccinated with rts,sas01e and protection against p falciparum clinical malariacircumsporozoite-specific t细胞反应在儿童接种rts,sas01e和防止p恶性疟原虫疟疾临床.pdfVIP

Circumsporozoite-Specific T Cell Responses in Children Vaccinated with RTS,S/AS01E and Protection against P falciparum Clinical Malaria 1 2 1 2 1 2 Ally Olotu , Philippe Moris , Jedidah Mwacharo , Johan Vekemans , Domtila Kimani , Michel Janssens , 1 2 2 2 3,4 3 Oscar Kai , Erik Jongert , Marc Lievens , Amanda Leach , Tonya Villafana , Barbara Savarese , Kevin 1,5 2 1,5 Marsh , Joe Cohen , Philip Bejon * 1 Kenya Medical Research Institute/ Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, Kilifi, Kenya, 2 GlaxoSmithKline Biologicals, Rixensart, Belgium, 3 PATH Malaria Vaccine Initiative (MVI), Bethesda, Maryland, United States of America, 4 MedImmune, LLC, Gaithersburg, Maryland, United States of America, 5 Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract Background: RTS,S/AS01E is the lead candidate pre-erythrocytic malaria vaccine. In Phase IIb field trials the safety profile was acceptable and the efficacy was 53% (95%CI 31%–72%) for protecting children against clinical malaria caused by P. falciparum. We studied CS-specific T cell responses in order to identify correlates of protection. Methods and Findings: We used intracellular cytokine staining (for IL2, IFNc, and TNFa), ex-vivo ELISPOTs (IFNc and IL2) and IFNc cultured ELISPOT assays to characterize the CS-specific cellular responses in 407 children (5–17 months of age) in a phase IIb randomized co