Vaccine Safety and Human Genetic Variations

Serious health problems following vaccination are rare, even though millions of people are vaccinated every year in the United States. Why do only a small number of people develop these health problems, called vaccine-associated adverse events (VAEs)? Do they have genetically determined differences in their immune responses to vaccination, compared to those who do not experience adverse events?

Few studies have been published on the genetic risk factors for VAEs. CDC has lead responsibility for monitoring the safety of vaccines licensed for use in the U.S., and for performing research to inform safe vaccination practices. So CDC is working with partners to study the relationship between human genetics and vaccine safety.

Identifying genetic associations and risk of serious VAEs eventually may allow—

• Screening for markers of susceptibility.
• Improved guidance for vaccination.
• Development of safer vaccines.

ISO’s Genomics Initiative

CDC's Immunization Safety Office (ISO) is developing a genomics initiative to—

• Develop a scientific approach to understanding the genetic basis for VAEs and their proper public applications.
• Increase cooperation between federal agencies, academia, and industry.
• Perform studies to identify genes that may be associated with an increased risk for VAEs.
• Identify strategies for integrating genomics into vaccine safety.

This initiative's long-term goal is to identify genetic features that can be determined before vaccination, so doctors can tailor vaccine schedules to the patient's personal risk.

On January 30 and 31, 2008, ISO held a conference titled "Understanding the Genomic Basis of Vaccine Safety" that brought together representatives of CDC, the Food and Drug Administration, the Department of Defense's Vaccine Healthcare Centers Network, research universities, and vaccine manufacturers. The conference discussed a systematic approach to research into the genetics of immunization safety.

Studies

There is increasing appreciation for how human genetic variation may affect the risk for medication-related and vaccine-related adverse events. While substantial research has been done on the genetic basis of medication safety, relatively little research has been done on the genetic basis of vaccine safety. ISO is sponsoring four studies on this issue—

• Post-Vaccine Adverse Events: Establishment of a Centralized Repository of Biological Specimens. This study will create a registry of clinically significant adverse events and related clinical data, and a repository of biological specimens from patients who experienced serious VAEs. To date, 68 specimens from 4 subjects have been stored in the bank.



• Evaluation of Genetic Risk Factors for Guillain-Barré Syndrome (GBS) After Vaccination. GBS has been associated with flu and MCV4 vaccines. Since GBS is rare, genetic predisposition may be an important contributing factor. This study will identify genes that may be associated with an increased risk of GBS after vaccination.



• The Genomics of Wheezing and Variable Immune Response After Influenza Vaccination in Children 6–59 Months of Age. Recent studies have shown that children's reaction to a flu vaccine may be controlled by certain genetic variants. This study will identify both genetic and non-genetic factors that can predict whether a person will have an adverse reaction to the flu vaccine.



• Rheumatoid Arthritis, Hepatitis B Vaccine, and Genetic Polymorphisms: Is There an Association? The family of immune response genes that are associated with an increased risk for rheumatoid arthritis (RA) also control a person's immune response to a hepatitis B vaccine. This study will examine the association between these genes and vaccine exposure in the development of RA.