Egg-Based Vaccines Less Protective Against Circulating Flu Viruses

A new study of the 2017-2018 influenza vaccine is bolstering concerns about the effectiveness of egg-grown flu vaccines and could help to spur research into more effective alternatives.

Investigators from the University of Michigan and the Centers for Disease Control and Prevention sought to unpack the relatively low level of influenza vaccine effectiveness during last flu season (40%, according to the CDC). To do so, they examined vaccination effectiveness through the lens of egg-grown versus cell-grown vaccines.

The investigators took serum samples from 15 individuals shortly after they were diagnosed with A(H3N2) influenza. As a control, investigators took similar samples from 15 adults who were hospitalized but who were not infected with influenza.

The team used microneutralization to measure titers against egg-grown and cell-grown vaccine strains, as well as a representative set of circulating flu viruses. The results add additional evidence to fears that egg-grown vaccines are less effective.

“Individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain and lower titers against circulating viruses,” wrote corresponding author Emily T. Martin, PhD, of the University of Michigan, and colleagues.

Martin and her team concluded in the study that titers against circulating viruses were protective, but titers against egg-adapted vaccine strains were not. Specifically, the team found that a two-fold increase in titers against the egg-grown vaccine strain did not have a statistically significant impact on influenza infection risk, but a similar increase in cell-grown titers against a circulating strain was effective at reducing flu risk.

Scientists have invested considerable time in recent years attempting to figure out why egg-grown vaccines seem to lag behind their cell-grown counterparts. Studies have shown that vaccine strains grown in eggs tend to mutate over time.

"Any influenza viruses produced in eggs have to adapt to growing in that environment and hence generate mutations to grow better," said Ian Wilson, DPhil, a professor of structural biology at the Scripps Research Institute, in California, in a press release.

Unfortunately, those adaptations mean the resulting vaccine is optimized to fight the egg-adapted version of influenza, and not necessarily the strain that is active in the area.

Wilson and colleagues published findings documenting the structural underpinnings of this phenomenon in October. Writing in PLOS Pathogens, Wilson and colleagues said the need to move beyond egg-based flu vaccines is urgent.

Wilson said cell-based methods are one alternative that seems to produce better vaccines. The CDC’s Advisory Committee on Immunization Practices echoed Wilson’s concerns in its report on the 2017-2018 flu season. While the vaccine still helped avert more than 80,000 hospitalizations, the committee wrote that its top priorities included understanding the impact of egg adaptations, figuring out the difference in effectiveness between egg-based and non-egg-based vaccines, and engineering “optimal vaccine viruses that have fewer disruptive egg-adaptive changes.”

Egg-based vaccines have been in use for 70 years. The Food and Drug Administration approved the first cell-based flu vaccine in 2016.

Martin did not respond to a request for comment from MD Magazine®. The titled, “Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season,” was published in The Journal of Infectious Diseases.