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


CONCLUSIONS
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.
Pulendran
Bali
B
Emory Vaccine Center, 954 Gatewood Rd., Atlanta, GA 30329, USA. bpulend@rmy.emory.edu
Miller
Joseph
J
Querec
Troy D
TD
Akondy
Rama
R
Moseley
Nelson
N
Laur
Oscar
O
Glidewell
John
J
Monson
Nathan
N
Zhu
Tuofu
T
Zhu
Haiying
H
Staprans
Sylvija
S
Lee
David
D
Brinton
Margo A
MA
Perelygin
Andrey A
AA
Vellozzi
Claudia
C
Brachman
Philip
P
Lalor
Susan
S
Teuwen
Dirk
D
Eidex
Rachel B
RB
Cetron
Marty
M
Priddy
Frances
F
del Rio
Carlos
C
Altman
John
J
Ahmed
Rafi
R
D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D014766:Viremia / Q000209:etiology* / Q000821:virology; D022341:Yellow Fever Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D015005:Yellow fever virus / Q000276:immunology*
D018946:Chemokine CCL5; D019713:Receptors, CCR5; D022341:Yellow Fever Vaccine