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Age and Gender Differences Seen in Immune System Response to the 2009 H1N1 Pandemic Influenza Virus

Scientists at the Food and Drug Administration (FDA) showed for the first time that individuals age 65 years and older had a more effective antibody response to the vaccine against the 2009 H1N1 pandemic influenza virus than did younger individuals.

The finding might help explain why public health officials found that the rate of illness and death during the 2009 H1N1 influenza pandemic was lowest in adults aged 65 years and above—a pattern similar to what occurred during the 1918 Spanish influenza pandemic.

Some scientists previously explained this observation by noting that elderly individuals likely had been exposed to 1918 H1N1-like viruses before 1930, or to the swine-origin H1N1 virus that caused an epidemic in 1976. Other scientists suggested that repeated vaccinations against seasonal strains of influenza had provided some protection against the new 2009 H1N1 virus.

Previous studies of the immune system response to influenza viruses used a technique called hemagglutinin inhibition assay (HI). Those studies were not able to detect this age difference in immune responses to the 2009 H1N1 virus.

For the current study, FDA scientists from the Center for Biologics Evaluation and Review (CBER) used laboratory techniques that enabled them to study more effectively how well anti-swine influenza virus antibodies worked. Specifically, they studied the ability of antibodies to recognize and bind to a specific protein on the 2009 H1N1 virus called HA1. HA1 is the globular head of a protein on the surface of the virus called hemagglutinin (HA). HA1 contains most of the targets that anti-H1N1 antibodies seek out during an immune system response. The antibodies were collected from individuals who participated in a clinical trial that studied the effectiveness of the 2009 H1N1 pandemic influenza vaccine in both young and elderly adults.

The scientists used a technique called genome-fragment phage display libraries (GFPDL) to determine which parts of the virus each type of antibody attacked. Then they used a technique called Surface Plasmon Resonance (SPR) to determine how long antibodies stayed bound to their targets—another measure of how efficient the antibodies are. The CBER scientists found that the H1N1 vaccine induced 10-fold higher antibody levels in elderly compared to younger adults. These antibodies primarily targeted the HA1 globular head, including the structure the virus uses to bind to cells that it infects.

Importantly, the antibodies from elderly individuals bound the HA1 protein much stronger than antibodies from younger adults. This high-affinity binding is typical of so-called “long term memory” responses. Long-term memory refers to those antibody-producing cells that were originally activated by circulating influenza viruses or vaccination and have matured so they are “on alert.” Such cells can very quickly release antibodies that will bind tightly to their designated target, even if the infection occurs many months or years later. Such highly effective antibodies are likely to have helped fight off the pandemic influenza virus, especially early after infection, and would likely be effective against seasonal strains of H1N1.

The CBER scientists also reported for the first time that women under 65 years of age developed antibodies that bound less strongly to HA1 compared to men in the same age group. This finding may explain reports on higher infection rates among young women during the H1N1 2009 influenza pandemic.

The technologies used in the current study are likely to improve the ability of CBER scientists to understand why new influenza vaccines work differently in different populations. This will be especially important as new types of vaccines are developed and evaluated by FDA.

Article

“Immune response following H1N1pdm09 vaccination: differences in antibody repertoire and avidity in young and elderly populations stratified by age and gender”

The Journal of Infectious Diseases; first published online December 29, 2011
doi:10.1093/infdis/jir791

Authors

Surender Khurana, Nitin Verma, Kawsar R. Talaat2, Ruth A. Karron2›, and Hana Golding1›

1Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, MD 20892; 2Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.

S.K. and N.V. contributed equally to this manuscript

R.K and H.G. contributed equally to this manuscript