Antibody Levels Comparable in Cell-, Egg-Based Flu Vax in Kids

WASHINGTON — There was no difference in antibody response, including hemagglutination inhibition assay (HAI) and microneutralization titers, between egg-based and cell-cultured influenza vaccine in children, a researcher said here.

A randomized trial found no significant differences in response to a variety of strains, including influenza A H1N1 and H3N3 and influenza B viruses for a small group of children who were randomized to receive either egg-based or cell-based flu vaccine in fall 2018-2019, reported Richard Zimmerman, MD, of the University of Pittsburgh in Pennsylvania, at a late-breaking presentation at the IDWeek meeting, with joint sponsorship by the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, the Society for Healthcare Epidemiology of America (SHEA), and the HIV Medicine Association.

He noted that in 2018-2019, for the first time, three of the four components of cell-culture inactivated influenza vaccine (or Flucelvax) were based on World Health Organization cell-based strains compared with only one cell-based strain (H3N2) in the previous year.

“Influenza vaccine effectiveness varies by strain, by age group, and by season [and] one vaccine efficacy improvement effort is focused on reducing egg adaptations through alternate manufacturing techniques,” Zimmerman said.

While not involved with the research, Andrew Pavia, MD, chief of pediatric infectious diseases at the University of Utah in Salt Lake City, provided some context, citing some of the many limitations of the egg-based flu vaccine.

“We can’t ramp up egg-based vaccine production,” Pavia, who was not involved in the study, told MedPage Today. “One of the real reasons we want cell-cultured vaccine is it can be scaled up in a pandemic. And in some seasons, the adaptations that the virus has to go through in the egg either make it less immunogenic or can lead to very slow production.”

Pavia cited the example of the 2017-2018 flu season, which was the last severe flu season in the U.S. He said that one of the problems of the vaccine that year is that people who received the vaccine “made a ton of antibodies” that was very effective at killing the type of virus that was grown in eggs, “but that was significantly different than the wild-type virus they were getting,” noted Pavia, who is co-chair of the Infectious Diseases Society of America (IDSA) Treatment Guidelines Panel.

“But if we keep doing the same thing for 65 years and it doesn’t work perfectly, it’s probably time to move on,” he said.

Notably, the U.S. government appears to be moving on from egg-based flu vaccines, as President Trump recently signed an executive order that calls for expanding capacity for alternative flu vaccines, such as cell-based vaccines.

Zimmerman and colleagues randomized a group of healthy children, ages 4-20 years, from five primary care clinics, with no known allergies to vaccine components, to receive either the quadrivalent inactivated cell-based vaccine (Flucelvax) or the inactivated egg-based vaccine (Fluzone).

Blood draws were done at day 0 (pre-vaccination), as well as day 7 and day 28, post-vaccination, and done before significant circulation of influenza in the community.

Overall, data from 148 children was analyzed — 75 in the cell-based group and 73 in the egg-based group. Nearly all were ages 9-20 years, and about half were girls in both groups. About 80% were non-white, and more than three-quarters of both groups had public insurance. About 55% to 61% had been immunized with inactivated influenza vaccine in the prior flu season.

HAI serology was similar between groups across influenza strains (influenza A H1N1, B Victoria, B Yamagata). Microneutralization antibody responses were also comparable for H3N2 in cell and egg viruses.

Not surprisingly, there was substantially higher seroconversion among participants who had not been vaccinated in 2017-2018.

However, Zimmerman concluded that “this requires a lot more in-depth analysis than just looking at HAI.”

“This study shows us just how complex it is to start learning about which vaccines work better,” Pavia said.

Indeed, he characterized this study as a “first step” on the way to comparing the actual clinical effectiveness of egg-based and cell-culture based vaccines.

“Not every company is going to do a 20,000-person randomized clinical trial every time they improve the flu vaccine,” Pavia noted. “So we in the flu community have to do effectiveness studies to compare vaccines, and that’s more difficult.”