Vaccines, Blood & Biologics

Immune system enzyme is key to optimal antibody responses against influenza virus


Scientists at the U.S. Food and Drug Administration (FDA) in collaboration with scientists at the University of Miami Miller School of Medicine (Miami, FL) showed for the first time that the decreased level of activity of a key immune system enzyme with increasing age is correlated with a reduction in the response to H1N1 pandemic influenza vaccine.
The enzyme, called activation-Induced cytidine-deaminase (AID), is critical to the ability of the immune system’s B cells to mature into antibody-secreting cells in response to vaccination. Although it was already known that the level of this enzyme decreases with age, the full impact of this decline was not fully appreciated until now.
 The scientists demonstrated that there is a significant difference in AID levels between young and older adults, with a gradual drop in AID activity observed between 50-85 years. This decline in AID response after vaccination is correlated with a decline in the ability of the immune system to “redesign” antibodies so they become increasingly more effective against influenza. This process, called antibody affinity maturation, is necessary for the immune system to launch a strong response to vaccination. It also enables the immune system to produce “immunological memory,” that is, immune cells that “remember” the vaccination even years later and are primed to respond to the influenza virus.
These findings are important because they suggest that the decreasing levels of AID activity in older adults might affect the ability of a new vaccine to trigger an effective immune response. This finding could inform the design of future clinical trials to assess effectiveness of vaccines in the elderly.
The FDA scientists are with the Office of Vaccines Research and Review at the Center for Biologics Evaluation and Research.

“AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in vivo following pandemic 2009-H1N1 vaccination in humans”
PLoS Pathogens
published 13 Sept. 2012
Surender Khurana1*, Daniela Frasca2, Bonnie Blomberg2, Hana Golding1*
1Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluatino and Research, Food and Drug Administration, Bethesda, MD, 20892; 2Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101.

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