The immunogenetics of smallpox vaccination.
We hypothesized that individuals who develop fever after smallpox vaccination have genetically determined differences in their immune responses to vaccinia virus. We looked for an association between the development of fever and single-nucleotide polymorphisms (SNPs) in 19 candidate genes in 346 individuals previously assessed for clinical responses to smallpox vaccination. Fever after smallpox vaccination is associated with specific haplotypes in the interleukin (IL)-1 gene complex and in the IL18 gene. A haplotype in the IL4 gene was highly significant for reduced susceptibility to the development of fever after vaccination among vaccinia-naive individuals. Our results indicate that certain haplotypes in the IL-1 gene complex and in IL18 and IL4 predict an altered likelihood of the development of fever after smallpox vaccination. Our findings also raise the possibility that these same haplotypes may identify individuals at risk for the development of fever after receipt of other live virus vaccines, providing information that could be useful in anticipating and preventing more-serious adverse events.
Stanley
Samuel L
SL
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. stanleys@msnotes.wustl.edu
Frey
Sharon E
SE
Taillon-Miller
Patricia
P
Guo
Jianhua
J
Miller
Raymond D
RD
Koboldt
Daniel C
DC
Elashoff
Michael
M
Christensen
Ryan
R
Saccone
Nancy L
NL
Belshe
Robert B
RB
D000328:Adult; D005260:Female; D005334:Fever / Q000235:genetics* / Q000276:immunology / Q000821:virology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics; D012900:Smallpox Vaccine / Q000009:adverse effects* / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects*; D014613:Vaccines, Attenuated / Q000009:adverse effects* / Q000276:immunology
C508590:IL1R1 protein, human; C508598:IL4 protein, human; D007375:Interleukin-1; D020382:Interleukin-18; D053573:Receptors, Interleukin-1 Type I; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; D015847:Interleukin-4