Case of yellow fever vaccine--associated viscerotropic disease with prolonged viremia, robust adaptive immune responses, and polymorphisms in CCR5 and RANTES genes.

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.

• Authors: Bali Pulendran, Joseph Miller, Troy D Querec, Rama Akondy, Nelson Moseley, Oscar Laur, John Glidewell, Nathan Monson, Tuofu Zhu, Haiying Zhu, Sylvija Staprans, David Lee, Margo A Brinton, Andrey A Perelygin, Claudia Vellozzi, Philip Brachman Jr, Susan Lalor, Dirk Teuwen, Rachel B Eidex, Marty Cetron, Frances Priddy, Carlos del Rio, John Altman, Rafi Ahmed
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 198 Issue 4 Pg. 500-7 (Aug 15 2008) ISSN: 0022-1899 [Print] United States
• PMID: 18598196 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Chemokine CCL5
• Receptors, CCR5
• Yellow Fever Vaccine

Topics

• Chemokine CCL5 (genetics, metabolism)
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic
• Receptors, CCR5 (genetics, metabolism)
• Viremia (etiology, virology)
• Yellow Fever Vaccine (administration & dosage, adverse effects)
• Yellow fever virus (immunology)