Duration of post-vaccination humoral immunity against yellow fever in children.

INTRODUCTION: Vaccination is the most important measure for prevention and control of yellow fever. It is recommended by the World Health Organization (WHO) for residents of endemic areas and travelers to risk areas. In 2013, the WHO discontinued the recommendation of booster doses every 10 years, indicating a single dose as sufficient for lifelong protection. OBJECTIVE: Considering the lower immune response to YF vaccine in children compared to adults, this study was set out to assess the duration of immunity to YF in children vaccinated in the first two years of life. METHODS: This cross-sectional study involved children aged 9 months to 12 years with accessible vaccination records recruited in primary care units from a metropolitan area in Southeast Brazil. The serologic status (negative, indeterminate and positive), and geometric mean titers (GMT, inverse dilution) of neutralizing antibodies against YF obtained by Plaque Reduction Neutralization Test was assessed across categories of time after YF vaccination. The strength of association of seropositivity with time was assessed by the odds ratio (OR) taking recent vaccination (1-6 months) as reference. RESULTS: A total of 824 children recruited from August 2010 to July 2011were tested. The proportion of seropositivity (95% C.I.) and GMT (95% C.I.) dropped markedly across time periods: from 86.7% (80.5-91.4%), GMT 47.9 (38.3-59.9) in newly vaccinated to 59.0% (49.7-67.8%), GMT 14.8 (11.6-19.1) and 42.2% (33.8-51.0), GMT 8.6 (7.1-12.1), respectively in the subgroups vaccinated 31-72 months and 73-100 months before. CONCLUSIONS: Analogous to previous findings in adults, these data support the need for revaccination of children living in areas with yellow fever virus circulation in humans or in other primates. The data also supported the change of a booster dose to 4 years of age for those primarily vaccinated for yellow fever in the first two years of life.

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-α⁺ 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⁺).