Cytokine Signatures of Innate and Adaptive Immunity in 17DD Yellow Fever Vaccinated Children and Its Association With the Level of Neutralizing Antibody

Background. The live attenuated yellow fever (YF) vaccines have been available for decades and are considered highly effective and one of the safest vaccines worldwide. Methods. The impact of YF-17DD-antigens recall on cytokine profiles of YF-17DD-vaccinated children were characterized using short-term cultures of whole blood samples and single-cell flow cytometry. This study enrolled seroconverters and nonseroconverters after primovaccination (PV-PRNT(+) and PV-PRNT(-)), seroconverters after revaccination (RV-PRNT(+)), and unvaccinated volunteers (UV-PRNT(-)). Results. The analysis demonstrated in the PV-PRNT(+) group a balanced involvement of pro-inflammatory/regulatory adaptive immunity with a prominent participation of innate immunity pro-inflammatory events (IL-12(+) and TNF-alpha(+) NEU and MON). Using the PV-PRNT(+) cytokine signature as a reference profile, PV-PRNT(+) presented a striking lack of innate immunity proinflammatory response along with an increased adaptive regulatory profile (IL-4(+) CD4(+) T cells and IL-10(+) and IL-5(+) CD8(+) T cells). Conversely, the RV-PRNT(+) shifted the overall cytokine signatures toward an innate immunity pro-inflammatory profile and restored the adaptive regulatory response. Conclusions. The data demonstrated that the overall cytokine signature was associated with the levels of PRNT antibodies with a balanced innate/adaptive immunity with proinflammatory/regulatory profile as the hallmark of PV-PRNT(MEDIUM+), whereas a polarized regulatory response was observed in PV-PRNT(-) and a prominent proinflammatory signature was the characteristic of PV-PRNT(HIGH+).Bio-Manguinhos/Oswaldo Cruz Foundation (FIOCRUZ)[05/05]Bio-Manguinhos/Oswaldo Cruz Foundation (FIOCRUZ)[05/08]Bio-Manguinhos/Oswaldo Cruz Foundation (FIOCRUZ)[009/2010]Council for Scientific and Technological Development (CNPq)[479663/2004-1]Council for Scientific and Technological Development (CNPq)[308651/2006-5]Council for Scientific and Technological Development (CNPq)[472782/2009-6]Council for Scientific and Technological Development (CNPq)[303316/2009-8]Minas Gerais State Research Foundation (FAPEMIG)[APQ 01183-08]Minas Gerais State Research Foundation (FAPEMIG)[APQ 01877-10]Minas Gerais State Research Foundation (FAPEMIG)[PDJ 00265-09]National Council for Scientific and Technological Development (CNPq