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To investigate the underlying immunologic mechanism, we analyzed the B and T peripheral follicular helper cell (pTfh) responses. Here, we show that protection in both study arms was associated with early induction of functional IL-21-secreting circumsporozoite (CSP)-specific pTfh cells, together with induction of CSP-specific memory B cell responses after the second dose that persisted after the third dose. Data integration of key immunologic measures identified a subset of non-protected individuals in the standard (STD) vaccine arm who lost prior protective B cell responses after receiving the third vaccine dose. We conclude that the DFD regimen favors persistence of functional B cells after the third dose.<\/jats:p>","DOI":"10.7554\/elife.51889","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T20:00:19Z","timestamp":1588017619000},"source":"Crossref","is-referenced-by-count":56,"title":["A delayed fractionated dose RTS,S AS01 vaccine regimen mediates protection via improved T follicular helper and B cell responses"],"prefix":"10.7554","volume":"9","author":[{"given":"Suresh","family":"Pallikkuth","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidhartha","family":"Chaudhury","sequence":"additional","affiliation":[{"name":"Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, United States"},{"name":"Henry M. 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