Case of Yellow Fever Vaccine-Associated Viscerotropic Disease with Prolonged Viremia, Robust Adaptive Immune Responses, and Polymorphisms in CCR5 and RANTES Genes

• Type of Material: Article
• Authors: Bali Pulendran, Emory University; Joseph Miller, Emory University; Troy D. Querec, Emory University; Rama Akondy, Emory University; Nelson Moseley, Emory University; Oskar Laur, Emory University; John Glidewell, Emory University; Nathan Monson, Emory University; Tuofu Zhu, University of Washington; Haiying Zhu, University of Washington; Sylvija Staprans, Emory University; David Lee, Emory University; Margo A. Brinton, Georgia State University; Andrey A. Perelygin, Georgia State University; Claudia J. Vellozzi, Emory University; Philip Sigmund Brachman Jr., Emory University; Susan Lalor, Emory University; Dirk Teuwen, Sanofi Pasteur; Rachel B. Eidex, Centers for Disease Control and Prevention; Martin S. Cetron, Emory University; Frances Priddy, Emory University; Carlos Del Rio, Emory University; John D Altman, Emory University; Rafi Ahmed, Emory University
• Language: English
• Date: 2008-08-15
• Publisher: Oxford University Press (OUP): Policy A1 - Oxford Open Option C
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 by the Infectious Diseases Society of America. All rights reserved.
• Final Published Version (URL): http://jid.oxfordjournals.org/content/198/4/500
• Title of Journal or Parent Work: Journal of Infectious Diseases
• ISSN: 0022-1899
• Volume: 198
• Issue: 4
• Start Page: 500
• End Page: 507
• Grant/Funding Information: Financial support: National Institutes of Health (grants U19 AI05726601 to R.A. and B.P., R01 AI048638 to B.P., R01 DK057665 to B.P., U54 AI057157 to B.P., and U01 AI-50019 to B.P.).
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Pathology

Abstract

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+CD16bright monocytes to tissues. Consistent with this, there was a 200-fold increase in the number of CD14+CD16bright 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.