Ethnicity Affects Immune Response to Flu Vaccine

Dana-Farber Cancer Institute researchers indicate that the degree to which the influenza vaccine protects patients from the virus depends on their ethnic background and other inherited factors.

Published online on February 16 in the Nature journal, Scientific Reports, the study found unexpected ethnicity influences on genetic variation in a key immune system gene that generates antibodies that are able to recognize and fight the common influenza A virus.

The research team, led by Wayne Marasco, MD, PhD, a cancer immunologist and virologist at Dana-Farber, suggests that their findings could spawn the development of new tools that predict how various people and populations may respond to influenza vaccines. These insights, they said, will be paramount to continued efforts to create “universal” vaccines for providing multi-year protection against numerous flu strains.

“This will change our understanding of how to achieve universal vaccine responsiveness in a population,” Marasco said.

For the study, Marasco and colleagues explored variations in the IGHVI-69 germline gene, one of about 50 human genes that hold instructions for making millions of protein antibodies to fight infections. These antibodies recognize identifying molecules on virus particle surfaces and then call for “neutralizing” antibodies to block them.

The ability of the IGHVI-69 gene antibodies to bind to the “stem” of the lollipop-shaped protein hemagglutinin on the surface of the flu virus is what makes them potentially useful in the development of universal flu vaccines. Whereas current vaccines mostly cause the immune system to recognize the “head” of the hemagglutinin protein—which shape-shifts from year to year in order to avoid the effects of the flu vaccine—the stem is less susceptible to change.

Therefore, vaccines that utilize the IGHV1-69 genes would presumably lead to the creation of these types of stem antibodies that could eventually provide long-term protection against numerous flu strains.

The researchers conducted their study with the knowledge that the IGHV1-69 gene is very polymorphic and exists in 14 slightly different forms, with all people inheriting two variants, one from each parent. Some of these variants are more effective than others at setting up a response to the flu virus, or to a vaccine that mimics part of the virus.

Additionally, 15% to 20% of people do not carry effective versions of the gene and thus cannot make antibodies to the flu virus. Marasco explained that this is why current vaccines are well below 100% effective.

For the study, Marasco and colleagues assessed stored blood samples from patients who received a vaccine against the H5N1 flu virus in 2007. The team found in test tube experiments that the strength of one’s immune response varied significantly depending on which version of the IGHV1-69 gene they carried as well as how many copies of the genes they had.

The researchers also found that the frequency of various versions of the IGHV1-69 gene varied dramatically among African, Asian, and European ethnic groups. They recommend that future research in this area focus on building a complete catalogue of variations of all 50 antibody genes, including the IGHV1-69 gene, and map them to populations around the world.

Sequencing this region of the human genome using current next-generation DNA sequencing tools could help predict vaccine responsiveness on both individual and population levels. The study authors said this effort “will be particularly important for the development and monitoring of the next-generation ‘universal’ influenza vaccines” that are directed to the hemagglutinin stem region.