New Study Finds a Link between a Person's Ethnicity and Response to the Influenza Vaccine

Researchers from the Dana-Farber Cancer Institute in Boston, MA have, for the first time, identified a link between a person’s genetic make-up, as well as their ethnic background, and their response to influenza vaccine.

In a study published online by Nature, the researchers describe specific variations in the IGHV1-69 gene, influenced by a person’s ethnicity, that seem to mediate immune system response to the influenza A virus. The IGHV1-69 gene’s role in generating antibodies that recognize the influenza A virus and enable the immune system to respond to it has been well documented.

“We have known for many years that individuals in our [study] population respond differently to a given influenza vaccine, but the reasons for these differences have not been understood,” Wayne A. Marasco, MD, PhD, study co-author and Associate Professor, Department of cancer Immunology and AIDS, Dana-Farber Cancer Institute, told Contagion^®. “Our study provides new evidence that the genes that make anti-influenza antibodies have a significant influence on our ability to mount broadly neutralizing anti-influenza antibody responses.”

Dr. Marasco and his colleagues analyzed stored blood samples from 85 patients who received the H5N1 flu virus vaccine in 2007. They observed that responses to the vaccine varied significantly based on which of the 14 known alleles of the IGHV1-69 gene the study subjects carried. The authors noted that the various alleles of the gene “can be differentiated by the presence of either a phenylalanine or leucine at amino acid position 54 within the apex of the CDR-H2 loop.”

The researchers then studied antibody repertoires from the National Institutes of Health H5N1 vaccine cohort along with samples taken from the 1000 Genomes Project, a large-scale genome-sequencing database, and found that “the two allele families (phenylalanine or leucine) have markedly different effects on antibody repertoire expression that is in part explained by copy number variation,” with those with phenylalanine alleles possessing “higher levels of circulating IGHV1-69 Ab and HV1-69-sBnAb repertoires” than those with leucine alleles.

The researchers also found that the makeup and frequency of different versions of the IGHV1-69 gene varied by ethnic group. In analyzing samples from patients of African, Asian, and European descent, the authors noted that those of African descent appeared to be more likely to have the variation of the IGHV1-69 gene best equipped to fight the influenza A virus.

“Genetic variability in the locus of one heavy chain immunoglobulin germ-line gene called IGHV1-69 effects our ability to raise broadly neutralizing antibodies against the HA stem-domain, the type of antibodies that we would want in an ‘universal’ influenza vaccine,” Dr. Marasco told Contagion^®. “We also found that this genetic variability is different among different ethnic groups, [meaning] that not all individuals or ethnic populations will response in the same way to an influenza vaccine. In order to achieve ‘universal’ protection of all individuals and ethnic populations to influenza vaccines, we should know their genetic makeup in advance so that we can best match the influenza vaccine to the individual's genetic makeup.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.