Conference Coverage

Cell culture–based flu vaccine maintains immunogenicity



– Influenza vaccines that substitute flu grown in cell-culture for the standard formulation of flu grown in eggs recently came onto the U.S. market, and new evidence confirmed that cell-grown flu works at least as well as its egg-grown counterpart for triggering immune responses.

Dr. Richard K. Zimmerman, professor of family medicine, University of Pittsburgh

Dr. Richard K. Zimmerman

Results from a randomized study with 148 evaluable subjects that directly compared the immune response of individuals aged 4-20 years old to the 2018-2019 commercial formulation of a mostly cell-based influenza vaccine with a commercially marketed, fully egg-based vaccine from the same vintage showed “no difference” between the two vaccines for inducing serologic titers on both the hemagluttination inhibition assay and by microneutralization, Richard K. Zimmerman, MD, said at an annual scientific meeting on infectious diseases.

The question addressed by the study was whether the primarily cell culture–grown vaccine would perform differently in children than a standard, egg-grown vaccine. “We thought that we might find something different, but we didn’t,” said Dr. Zimmerman, a professor of family medicine at the University of Pittsburgh who studies vaccines. The finding gave further support to using flu vaccines made without eggs because of their advantages over egg-based vaccines, he said in an interview.

Dr. Zimmerman cited two major, potential problems with egg-grown influenza vaccines. First, they require a big supply of eggs to manufacture, which can pose logistical challenges that are absent with cell culture–grown vaccine once the bioreactor capacity exists to produce the necessary amount of cells. This means that egg-free vaccine production can ramp up faster when a pandemic starts, he noted.

Second, over time, egg-grown vaccine strains of influenza have become increasingly adapted to grow in eggs with the result that “in some years the egg-grown virus is so different as to not work as well [Proc Natl Acad Sci. 2017 Nov;114[44]:12578-83]. With cell culture you bypass” issues of glycosylation mismatch or other antigenic problems caused by egg passage, he explained.

Dr. Zimmerman feels so strongly about the superiority of the cell-culture vaccine that “I am personally going to get a vaccine that’s not egg based,” and he advised the University of Pittsburgh Medical Center to focus its 2019-2020 flu vaccine purchase primarily on formulations made by cell culture. For the 2019-2020 season, that specifically is Flucelvax, an inactivated influenza vaccine licensed for people aged at least 4 years old, and Flublok, a recombinant flu vaccine also produced entirely in cell culture and licensed for people aged at least 18 years old. The 2019-2020 season is the first one during which the quadravalent Flucelvax vaccine has all four component strains (one H1N1, one H3N2, and two B strains) grown in cell culture.

The study run by Dr. Zimmerman and associates at the start of the 2018-2019 season used that season’s formulation of Flucelvax, which had only three of its four component strains grown in cell culture plus one strain (H1N1) grown in eggs. The Pittsburgh researchers randomized 168 individuals to receive the 2018-2019 Flucelvax vaccine or Fluzone, an entirely egg-made quadravelent vaccine, and they had analyzable results from 148 of the enrolled participants, more than 85% of whom were 9-20 years old. The study’s primary endpoint was the extent of seropositivity and seroconversion 28 days after immunization measured with both a hemagglutination inhibition assay and by a microneutralization assay. The results showed similar rates in the 75 children who received Flucelvax and the 73 who received Fluzone. For example, seropositivity against B Victoria lineage strains by the hemagglutination inhibition assay 28 days after vaccination was 76% in children who received Flucelvax, and it was 79% among those who got Fluzone, with a seroconversion rate of 34% in each of the two study subgroups.

“These findings do not say that egg-free is better, but it was certainly no worse. My guess is that in some years vaccines that are egg-free will make a big difference. In other years it may not. But you don’t know ahead of time,” Dr. Zimmerman said.

The study received no commercial funding but received free Fluzone vaccine from Sanofi Pasteur. Dr. Zimmerman had no disclosures.

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