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November 06, 2017

Penn study pinpoints why last year's flu shot was a dud

Despite the usual barrage of seasonal warnings, fewer than 50 percent of Americans reported getting a flu shot last year. Public health officials generally advise most people to get it, especially the very young and elderly, but it turns out those who gambled last year may have been no worse off for skipping the vaccine.

New research from Penn's Perelman School of Medicine suggests the low efficacy of the 2016-17 flu shot — about 20 to 30 percent effectiveness, compared to an average of about 50-60 percent — was likely the result of a mutation in the H3N2 strain of the virus.

With viral strains adapting on a yearly basis, vaccine makers are left to predict not only how they will evolve, but how likely they are to produce an outbreak and at what point in the year.

Flu vaccines aim to protect us by priming our immune systems. When we're exposed to the proteins that form the outer layer of a killed flu virus, we generate antibodies that are ready to attack flu viruses whenever they reappear. Most of the vaccines we receive use purified proteins from a virus grown in chicken eggs, while others use antigens grown through alternative methods.

"Our experiments suggest that influenza virus antigens grown in systems other than eggs are more likely to elicit protective antibody responses against H3N2 viruses that are currently circulating," said Scott Hensley, an associate professor of microbiology at Penn. "The 2017 vaccine that people are getting now has the same H3N2 strain as the 2016 vaccine, so this could be another difficult year if this season is dominated by H3N2 viruses again."

The current strain of H3N2 emerged during the 2014-15 flue season and remains prevalent today. At some point during the development of last year's vaccine, the egg-grown protein acquired a mutation that reduced its effectiveness in warding off the live virus.

Hensley's team first looked at how antibodies in ferrets and humans responded to the egg-produced H3N2 strain in 2016-17, finding that the immune reaction was subpar. For comparison, they then look at how antibodies in both species reacted to the current circulating H3N2 strain using proteins developed in a non-egg system.

"Our data suggest that we should invest in new technologies that allow us to ramp up production of influenza vaccines that are not reliant on eggs," Hensley said. "In the meantime, everyone should continue to get their annual flu vaccine. Some protection against H3N2 viruses is better than nothing and other components of the vaccine, like H1N1 and influenza B, will likely provide excellent protection this year."

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