Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 198, Issue 4, Pages 500-507Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/590187
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Funding
- NCATS NIH HHS [UL1 TR000454] Funding Source: Medline
- NIAID NIH HHS [U19 AI05726601, U01 AI-50019, R01 AI048638, U19 AI057266, R01 AI056499, N01AI50019, U54 AI057157] Funding Source: Medline
- NIDDK NIH HHS [R01 DK057665] Funding Source: Medline
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Background. The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines. Despite its excellent safety record, some cases of viscerotropic adverse events develop, which are sometimes fatal. The mechanisms underlying such events remain a mystery. Here, we present an analysis of the immunologic and genetic factors driving disease in a 64-year-old male who developed viscerotropic symptoms. Methods. We obtained clinical, serologic, virologic, immunologic and genetic data on this case patient. Results. Viral RNA was detected in the blood 33 days after vaccination, in contrast to the expected clearance of virus by day 7 after vaccination in healthy vaccinees. Vaccination induced robust antigen-specific T and B cell responses, which suggested that persistent virus was not due to adaptive immunity of suboptimal magnitude. The genes encoding OAS1, OAS2, TLR3, and DC-SIGN, which mediate antiviral innate immunity, were wild type. However, there were heterozygous genetic polymorphisms in chemokine receptor CCR5, and its ligand RANTES, which influence the migration of effector T cells and CD14(+)CD16(bright) monocytes to tissues. Consistent with this, there was a 200-fold increase in the number of CD14(+)CD16(bright) monocytes in the blood during viremia and even several months after virus clearance. Conclusion. In this patient, viscerotropic disease was not due to the impaired magnitude of adaptive immunity but instead to anomalies in the innate immune system and a possible disruption of the CCR5-RANTES axis.
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