Abstract
The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV((D0))] and after vaccination (Day 30-45) [Primary Vaccinees, PV((D30-45))]. Data demonstrated high levels of neutralizing antibodies for PV((D30-45)) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV((D30-45)), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV((D30-45)) as compared to NV((D0)) (532vs398). Moreover, PV((D30-45)) exhibited increased levels of Terminal Effector (CD45RA(+)CCR7(-)) CD4(+) and CD8(+) T-cells and Non-Classical memory B-cells (IgD(+)CD27(+)). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV((D30-45)) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.