January 12, 2011
NIAID WEB BULLETIN
Antibodies Identified after 2009 H1N1 Infection Neutralize Multiple Flu Virus Strains
Findings Offer Clues for Universal Flu Vaccine
By analyzing blood samples taken from a small group of people infected with the 2009 H1N1 influenza virus, scientists have identified antibodies that can neutralize multiple influenza strains in laboratory experiments and also protect mice from disease. These data add to other evidence suggesting that the development of a universal influenza vaccine may be possible.
The study findings are reported online January 10th in the Journal of Experimental Medicine, by a team of investigators led by Rafi Ahmed, Ph.D., of Emory University in Atlanta, and Patrick Wilson, Ph.D., of the University of Chicago, and included scientists from Harvard and Columbia Universities and the National Institute of Allergy and Infectious Diseases (NIAID). NIAID, part of the National Institutes of Health, supported the study. Additional support was provided by the American Recovery and Reinvestment Act of 2009.
The research team studied blood samples from nine patients, ranging in age from 21 to 45 years old, diagnosed with 2009 H1N1 influenza. The samples were taken approximately 10 days after the onset of infection in these patients, who represented a range of illness, from mild to severe symptoms.
The investigators homed in on these patients’ blood plasmablasts, antibody-producing cells that appear shortly after infection. When the antibodies produced by these cells were analyzed, a surprisingly large number were found to be cross-reactive, that is, they could neutralize many different strains of influenza virus, including multiple seasonal H1N1 viruses, the 1918 H1N1 pandemic virus, and a disease-causing H5N1 avian influenza virus. Further study showed that these antibodies bound to specific sites on the hemagglutinin molecule, a protein that is attached to the surface of the influenza virus via a stem-like region. Interestingly, most of these cross-reactive antibodies bound to the stem-like region, which is known to vary little from strain to strain. Thus, in contrast to vaccination against seasonal influenza, infection with the 2009 H1N1 virus resulted in an unusually large cross-reactive antibody response.
In laboratory experiments, these antibodies protected cells from becoming infected with several different influenza viruses. Moreover, at least two of these antibodies could protect mice against lethal doses of the 2009 H1N1 influenza virus as well as two other laboratory strains of influenza, even when the antibodies were given two days after infection.
The investigators speculate that multiple exposures to seasonal influenza viruses and influenza vaccines over the years have given rise to memory cells that recognize the conserved regions of the virus. After a person is infected with 2009 H1N1, these cells become the source of antibody-producing plasmablasts. While broadly neutralizing antibodies have rarely been seen in people after exposure to seasonal viruses or vaccines, this study suggests that the outcome of 2009 H1N1 infection is different. Overall, the study shows that 2009 H1N1 can induce broadly protective human antibodies that bind to parts of the influenza virus that vary little from strain to strain, providing a potential immune target for use in a universal influenza vaccine.
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Last Updated January 12, 2011
Last Reviewed January 12, 2011