Immune response to flu vaccine linked to recipients' ethnic background

February 16, 2016
Credit: National Cancer Institute

How well a flu shot protects you from the virus can depend on your ethnic background and other inherited factors, report Dana-Farber Cancer Institute scientists.

The researchers, led by Wayne Marasco, MD, PhD, a cancer immunologist and virologist at Dana-Farber, found unexpected ethnicity influences on genetic variation in a key immune system gene that generates antibodies that can recognize and ward off the common influenza A virus.

The results could lead to new tools for predicting how different individuals and populations will respond to influenza vaccines, according to a report in the Nature journal, Scientific Reports. Additionally, the authors said, these insights will be important in ongoing efforts to develop "universal" vaccines that would provide multi-year protection against a wide variety of .

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

The study focused on variations in IGHV1-69, one of about 50 human genes carrying the instructions for making millions of protein antibodies to fight infections. The antibodies patrol the body and recognize identifying molecules on the surface of virus particles, then summoning "neutralizing" antibodies to block them.

Antibodies generated by the IGHV1-69 gene could be useful in developing universal flu vaccines. That's because these antibodies bind to the "stem" of a lollipop-shaped protein, hemagglutinin, on the flu virus' surface. Current vaccines largely cause the immune system to recognize the "head" of the hemagglutinin protein, but the flu virus rapidly shape-shifts this region from year to year to escape the vaccine. The stem, however, is less susceptible to change - and designing vaccines that makes better use of the IGHV1-69 genes should lead the body to make these types of stem antibodies that someday might offer long-term protection against many flu strains.

The IGHV1-69 gene is highly polymorphic and exists in 14 slightly different forms: each person inherits two of these variant forms, one from each parent.

Some versions of the gene are more effective than others at mounting a response to the - or to a vaccine made to mimic part of the virus. And about 15-20 percent of people don't actually carry the effective versions of this gene to make to the virus - they use some other genes that scientists haven't yet fully identified. That's one of the likely reasons why current vaccines are far less than 100 percent effective, Marasco explained.

The scientists studied stored blood samples from volunteers who received a vaccine against the H5N1flu virus in 2007. They found that in test tube experiments the strength of the individual's immune response varied significantly according to which version of the IGHV1-69 gene they carried, and also how many copies of the genes were present.

And they used other data to show that the frequency of different versions of the IGHV1-69 gene varied dramatically among three broad ethnic groups - African, Asian, and European. The scientists say it is the first report to link variations of the gene with .

In light of these new findings, the authors suggested that scientists should build a complete catalogue of variations of all 50 antibody including the IGHV1-69 gene and map them to populations across the globe. This region of the human genome has been deemed too complex to sequence using current next-generation DNA sequencing tools. However, doing so could prove useful for predicting vaccine responsiveness at the individual and population level.

In addition, they said, the 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.

Explore further: First flu exposure imprints itself on immune system

Related Stories

First flu exposure imprints itself on immune system

December 17, 2015
A person's first infection with the influenza virus likely stimulates the production of key antibodies that then shape later immune responses to different seasonal influenza strains. In a study published December 17th in ...

Video: Growing the flu in a laboratory

January 11, 2016
Early last year researchers at McMaster and the Icahn School of Medicine at Mount Sinai, New York announced that a universal flu vaccine could be on the horizon.

Study suggests potential hurdle to universal flu vaccine development may be overcome

August 15, 2012
In the quest for a universal influenza vaccine—one that elicits broadly neutralizing antibodies that can protect against most or all strains of flu virus—scientists have faced a sobering question: Does pre-existing ...

Fighting flu with designer drugs: A new compound fends off different influenza strains

February 4, 2016
A study published on February 4th in PLOS Pathogens reports that a new antiviral drug protects mice against a range of influenza virus strains. The compound seems to act superior to Oseltamivir (Tamiflu) and independent of ...

Knowing origin of broadly neutralizing antibodies could aid universal flu vaccine design

August 29, 2012
National Institutes of Health scientists have identified how a kind of immature immune cell responds to a part of influenza virus and have traced the path those cells take to generate antibodies that can neutralize a wide ...

Infant-friendly flu vaccine developed with key protein

January 19, 2016
According to the World Health Organization, influenza causes serious illness among millions of people each year, resulting in 250,000 to 500,000 deaths. Those most at risk include infants younger than six months, because ...

Recommended for you

The skinny on lipid immunology

October 20, 2017
Phospholipids - fat molecules that form the membranes found around cells - make up almost half of the dry weight of cells, but when it comes to autoimmune diseases, their role has largely been overlooked. Recent research ...

Bacterial pathogens outwit host immune defences via stealth mechanisms

October 20, 2017
Despite their relatively small genome in comparison to other bacteria, mycoplasmas can cause persistent and often difficult-to-treat infections in humans and animals. An extensive study by researchers from Vetmeduni Vienna ...

Scientists find where HIV 'hides' to evade detection by the immune system

October 19, 2017
In a decades-long game of hide and seek, scientists from Sydney's Westmead Institute for Medical Research have confirmed for the very first time the specific immune memory T-cells where infectious HIV 'hides' in the human ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Researchers release the brakes on the immune system

October 18, 2017
Many tumors possess mechanisms to avoid destruction by the immune system. For instance, they misuse the natural "brakes" in the immune defense mechanism that normally prevent an excessive immune response. Researchers at the ...

How cytoplasmic DNA triggers inflammation in human cells

October 17, 2017
A team led by LMU's Veit Hornung has elucidated the mechanism by which human cells induce inflammation upon detection of cytoplasmic DNA. Notably, the signal network involved differs from that used in the same context in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.