Abstract
The most recent Zaire Ebolavirus (ZEBOV) outbreak was the largest and most widespread in recorded history, emphasizing the need for an effective vaccine. Here, we analyzed human cellular immune responses induced by a single dose of the rVSV-ZEBOV vaccine candidate, which showed significant protective efficacy in endemic populations in Guinea. This is the first in-depth characterization of ZEBOV-GP specific, circulating follicular T cells (cTfh). Since antibody titers correlated with protection in preclinical models of ZEBOV infection, Tfh were predicted to correlate with protection. Indeed, the ZEBOV-specific cTfh data correlated with antibody titers in human vaccines and unexpectedly with the Tfh17 subset. The combination of two cutting edge technologies allowed the immuno-profiling of rare cell populations and may help elucidate correlates of protection for a variety of vaccines.
Highlights
The most recent Zaire Ebolavirus (ZEBOV) outbreak was the largest and most widespread in recorded history, emphasizing the need for an effective vaccine
(2) For cohort 2, there are two clusters of cytokines that show correlations: Cluster One consists of IL-2, IL-6, IL-12 and IL-13 while Cluster Two consists of IL-1β, IL-4, IL-10, and TNF-α
While the cluster of IL1β, IL-4, IL-10 and TNF-α is detected in all three cohorts, the basic cluster of IL-2, IL-12, IL-13 only becomes apparent in cohort 2
Summary
The most recent Zaire Ebolavirus (ZEBOV) outbreak was the largest and most widespread in recorded history, emphasizing the need for an effective vaccine. We analyzed human cellular immune responses induced by a single dose of the rVSV-ZEBOV vaccine candidate, which showed significant protective efficacy in endemic populations in Guinea This is the first in-depth characterization of ZEBOV-GP specific, circulating follicular T cells (cTfh). EVD was first reported in 1976 in two simultaneous outbreaks, in Sudan, and the Democratic Republic of Congo (DRC) where two distinct species of Ebolavirus, Zaire Ebolavirus (ZEBOV) and Sudan Ebolavirus (SEBOV) were associated with the significant outbreaks[4], the most recent outbreak exceeded all previous epidemics in terms of geographic range and number of cases[3] Even though this disease is associated with a high fatality rate, prophylaxis and treatment options remain scant and have not been fully evaluated for clinical efficacy. The current study establishes highly detailed immunoprofiles for a cohort of V920-immunized human subjects (for description of the clinical study, see ref. 13) and the tools and parameters which will allow a comparison with responses in ZEBOV- exposed humans, informing assessments of the immune response that may subsequently be applied to the identification of immune correlates of protection
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