Last year’s influenza vaccine has egg on its face, having demonstrated only 20% to 30% effectiveness—a low level of performance attributed to an adaptive mutation that affected egg-grown vaccines, but not vaccines that were produced in non-egg systems. The adaptive mutation, which was uncovered by scientists based at the University of Pennsylvania School of Medicine, affects a hemagglutinin (HA) protein that occurs in H3N2 viruses.
Due to the mutation, most people receiving the egg-grown vaccine did not have immunity against H3N2 viruses that circulated last year. “The 2017 vaccine that people are getting now has the same H3N2 strain as the 2016 vaccine,” noted Scott Hensley, Ph.D., an associate professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania. “So, this could be another difficult year if this season is dominated by H3N2 viruses again.”
Dr. Hensley is the senior author of a study that identified the mutation. This study (“Contemporary H3N2 Influenza Viruses Have a Glycosylation Site That Alters Binding of Antibodies Elicited by Egg-Adapted Vaccine Strains”) appeared November 6 in the Proceedings of the National Academy of Sciences.
“Our experiments,” Dr. Hensley emphasized, “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.”
During the 2014–2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today,” wrote the article’s authors. “The 2016–2017 seasonal influenza vaccine was updated to include a clade 3C.2a H3N2 strain; however, the egg-adapted version of this viral strain lacks the new putative glycosylation site. Here, we biochemically demonstrate that the HA antigenic site B of circulating clade 3C.2a viruses is glycosylated.”
Flu vaccines work by priming the immune system with purified proteins from the outer layer of killed flu viruses. This induces immune cells to make antibodies that stop foreign invaders from infecting cells, readying them to attack flu viruses when the body sees them again. Most flu vaccine proteins are purified from a virus grown in chicken eggs, although a small fraction of flu vaccine proteins are produced in systems that do not involve eggs.
“We show that antibodies elicited in ferrets and humans exposed to the egg-adapted 2016–2017 H3N2 vaccine strain poorly neutralize a glycosylated clade 3C.2a H3N2 virus,” the PNAS paper’s authors added. “Importantly, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that possesses the glycosylation site) and humans vaccinated with baculovirus-expressed H3 antigens (that possess the glycosylation site motif) were able to efficiently recognize a glycosylated clade 3C.2a H3N2 virus.”
“Current H3N2 viruses do not grow well in chicken eggs, and it is impossible to grow these viruses in eggs without adaptive mutations,” Dr. Hensley explained.
Dr. Hensley’s team showed that antibodies elicited in ferrets and humans exposed to the egg-produced 2016–2017 strain did a poor job of neutralizing H3N2 viruses that circulated last year. However, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that contains the new protein) and humans vaccinated with a H3N2 vaccine produced in a non-egg system were able to effectively recognize and neutralize the new H3N2 virus.
“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,” Dr. Hensley asserted. “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.”
