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Gene activity studies classify response to flu vaccine

Every year, millions of people take the "flu shot," but some of them still get the flu.

Scientists at Baylor College of Medicine think the reason some people are protected by the vaccine and others are not may lie within individual genomes or genetic blueprints of each person and the genes that govern how cells mount an immune response when exposed to the influenza vaccine.

In a report in a recent issue of the Journal of Infectious Diseases, researchers led by Drs. John Belmont and Robert Couch of BCM studied gene activity in 92 men ages 18 to 40 who received an influenza vaccination that provided protection against three kinds of flu virus – the usual format for vaccines given the public.

Improving effectiveness

Influenza is an important public health problem, causing 250,000 to 500,000 deaths worldwide each year. In the United States, between 2 and 6 percent of the public contract influenza each year with an average of 225,000 hospitalized and 3,000 to 49,000 dying. Annual vaccination is important to halting the disease and improving the effectiveness of the vaccine is the aim of much research.

"This is an important first step not only in understanding how people respond to the influenza vaccine, but also in understanding response to vaccine overall," said Couch, professor of molecular virology and microbiology at Baylor and an expert in the field for 40 years.

When Couch, Belmont and their colleagues looked at the genes that respond at high levels to influenza vaccine in young, healthy adults, they found those involved in the interferon system – a system known to be involved in recovering from viral infections – were the most important along with genes that govern the immediate immune response to infection.

The vaccination affected the body in two phases. In the first 24 hours, the researchers saw increased levels of genes that activate interferon (an antiviral compound) regulate an immune protein called interleukin-6 and govern how antigens are presented and processed by the immune system.

494 gene signature

These factors helped researchers classify how great a response the body would mount against the infection in the 14-28 days after the vaccination. This response was represented by antibodies against the flu. The higher the level of the antibodies, the greater the protection.

In particular, Belmont and colleagues describe a 494 gene signature that classified how people responded to the vaccine. Those who respond best show early signs of activating the interferon response as well as genes that regulate how antigens (the identifying proteins on cells) are recognized and presented to the immune system.

"These kinds of studies – called systems biology – can help us develop new vaccines and adjuvants (drugs that boost immune response)," said Belmont, professor of molecular and human genetics and pediatrics at BCM.

Others who took part in the research include Kristine L. Bucasas, Dr. Luis M. Franco, Dr. Chad A. Shaw, Dr. Molly S. Bray, Janet M. Wells, Diane Niño of BCM and Drs. Nancy Arden and John M. Quarles of Texas A&M University System Health Science Center, College Station, Texas.

Funding for this work came from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and a Ruth L. Kirschstein National Research Service Award Pre-doctoral Training Grant.