A Delayed Fractionated Dose of RTS,S AS01 Vaccine Regimen Mediates Protection via Improved T Follicular Helper and B cell Responses
Journal Article - Open Access
BIOTECHNOLOGY HPC SOFTWARE APPLICATIONS INST FORT DETRICK MD FORT DETRICK United States
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Malaria-071, a controlled human malaria infection trial, demonstrated that administration of three doses of RTS,SAS01 malaria vaccine given at one-month intervals was inferior to a delayed fractional dose DFD schedule 62.5 percent vs 86.7 percent protection, respectively. 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.