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New Evidence Links Smallpox Vaccination Side Effects to Genetic Factors

Boffins have found new evidence that supports the link between genetic factors and certain adverse reactions related to smallpox vaccination .

Immunization with live virus particles, as in the smallpox vaccine, is sometimes found to cause reactions that range from fatigue to serious illness.

The study was conducted by a team of researchers led by Samuel L. Stanley Jr. at the Washington University, St. Louis University, and The Emmes Corporation.

As part of the study, researchers examined 346 individuals who had participated in previous smallpox vaccination trials, 94 of whom developed fevers after vaccination to test whether people who develop fever after vaccination have genetically determined differences in their immune responses compared to those who do not.

The study found that some individuals who were given stored smallpox vaccine, which uses live vaccinia virus, developed fevers.

Researchers identified a total of eight haplotypes in four different genes that were associated with altered susceptibility to fever after vaccination.

It is the first study to show that fever after smallpox vaccination is associated with specific gene clusters in the interleukin-1 (IL-1) gene complex on chromosome 2 and the interleukin-18 gene on chromosome 11.

The interleukins, and especially the IL-1 gene complex, are groups of molecules associated with inflammation and immune responses. The IL-1 gene complex, and especially the IL-1A gene, was the site most significantly associated with different risks of fever.

Vaccines are the safest and most effective way to prevent a number of very important childhood and adult diseases. Our work is designed to identify ways we might make vaccines even more acceptable in the future by discovering ways to further reduce the chance of minor adverse, Stanley said.

According to James E. Crowe Jr of Vanderbilt University Me dical Center the findings represent an important preliminary step in understanding the variations in host responses to vaccines, and further studies will be needed to replicate these findings, and to test other vaccines.

The long-term goal is to determine genetic features that could be determined prior to vaccination, allowing practitioners to modulate the vaccination plan according to risk. This type of practice, the goal of personalized predictive medicine, appears closer in feasibility than ever given the pace of genetic testing, Crowe said.

The findings of the study were published in the July issue of The Journal of Infectious Diseases.


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