Lack of antibody diversity can make older people more susceptible to the flu – ScienceDaily



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Influenza vaccine may be less effective in the elderly, as their B cells are less able to produce antibodies that can adapt to protect against new viral strains, researchers reported on February 19 in the journal Cell Host & Microbe. With age, B cells and the antibodies they secrete acquire fewer mutations that provide flexible protection against the ever-changing influenza virus.

"The major implication is that when a new influenza virus circulates among the elderly, they do not have the right tools to fight it because their antibodies are not so protective," says Patrick Wilson. , senior author of the study, from the University of Chicago. "Our results could be used by the vaccine community to make better vaccines and improve the protection of the elderly population."

It is thought that the adverse effect of aging on the immune system is a major cause of illness and death in the elderly by increasing susceptibility to bacterial, fungal and viral infections. The vast majority of influenza deaths occur in populations older than 65, and the antibody response of the elderly to influenza vaccination is significantly reduced. As a result, influenza is one of the leading causes of death in the elderly and the vaccine only protects a fraction of this population.

To understand the underlying mechanisms, Wilson and his team compared how B cells and antibodies in older and younger adults respond to vaccination with different strains of influenza. While B cells from younger subjects had a recent and ongoing accumulation of mutations, older people appeared to have a substantially fixed B cell repertoire, lacking recent adaptations allowing evolution of B cells into divergent strains of influenza.

In addition, the antibodies of the elderly are less powerful and less able to protect against the influenza virus. Older antibodies only target conserved proteins and structures of the influenza virus, with fewer mutations that would allow effective responses against evolving viral strains. In contrast, antibodies from younger people are better able to recognize newly mutated molecules in the influenza virus.

The results suggest that the antibodies of the elderly originate from early-life cross-reactivity memory B cells, with reduced adaptation to recent influenza virus strains. For example, 47% of antibodies produced in the elderly have linked to six strains or more of the influenza virus, compared to only 12% in young adults. In addition, the antibodies of the elderly had a greater affinity for historical strains that circulated during their childhood and a lower affinity for more contemporary strains.

Despite these observations, vaccination remains the best way to protect the elderly from infection with the influenza virus. "We are not saying that people should not be vaccinated or that current vaccines are useless for the elderly," said first author, Carole Henry, of the University of Chicago.

Currently, researchers are trying to understand the underlying biological basis of their observations. From a clinical point of view, the results suggest that vaccines leading to protective mutations in B cells should be a priority to improve immunity against influenza in the elderly. "Newer vaccines developed specifically for the elderly population are now on the market and could help induce more protective antibodies," Wilson said. "The next step will be to badess the adaptability of antibodies in elderly people immunized with these vaccines."

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