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Updated: May 9, 2026

Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Inherited IFNAR1 structural deficiency in severe adverse events following yellow fever vaccination
Tamiris Azamor1, Paul Bastard2, Andrea Marques Vieira da Silva3
1Laboratory of high complexity (LACIFF). Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Fiocruz, Rio de Janeiro, Brazil; Laboratory of Immunological Technology (LATIM). Instituto de Tecnologia em Imunobiológicos-Bio-Manguinhos. Fiocruz, Rio de Janeiro, Brazil.
Abstract:
Yellow fever virus (YFV) infection is life-threatening but preventable by the live-attenuated YFV 17D/17DD vaccine. Rare Adverse Events Following Immunization (AEFI-YF) involve Inborn Errors of Immunity (IEI), and auto-antibodies against type I interferons (IFNs). We conducted an integrative genetics and functional investigation of a Brazilian family with three siblings presenting AEFI-YF (two deceased), using whole exome sequencing (WES), and qPCR, molecular modeling, in vitro YFV-17D stimulation of leukocytes, cytokine quantification, immunophenotyping, and RNAseq. A novel homozygous IFNAR1 copy number variation (CNV Δ3-4-5) in the proband (heterozygous in five of 11 unaffected relatives) caused receptor dysfunction, suppressing baseline IFN responses but triggering inflammasome-driven innate cell activation upon YFV-17D exposure. This study underscores IFNAR1 deficiency's causality in AEFI-YF pathogenesis and provides mechanistical insights. Our findings advocate for precision vaccinology by screening relatives of AEFI-YF cases for type I IFN EIIs and auto-antibodies prior to live-attenuated vaccination.
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