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Abstract
A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naïve baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α+ and IFN-γ+ produced by CD4+ and CD8+ T-cells along with increasing levels of IL-10+CD4+T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naïve baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8+ memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors thank the program for technological development in tools for health-PDTIS-FIOCRUZ for the use of its facilities.
Funding
The authors thank Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Bio-Manguinhos/FIOCRUZ; PROEP/CPqRR/FIOCRUZ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Programa Nacional de Imunizações (PNI) – Ministério da Saúde Brazil, FIOTEC, PDTIS, CAPES and Secretaria de Vigilância em Saúde (SVS) for financial support. ACCA and JGCdR received financial support from CNPq MCTI/CNPQ/Universal 14/2014 (ACCA - Grant # 444417/2014-1 and JGCdR - Grant # 458134/2014-7). OAMF and ATC thank the CNPq for the fellowships (PQ).