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Cell- and egg-based flu vaccines provide similar immunogenicity, surprising researchers

Photo of Richard Zimmerman
Richard Zimmerman

WASHINGTON — Cell- and egg-based quadrivalent inactivated influenza vaccines have comparable immunogenicity for children aged 4 years and older, according to results from a randomized controlled trial presented at IDWeek.

Richard Zimmerman, MD, MPH, tenured professor of family medicine and clinical epidemiology at the University of Pittsburgh, told Infectious Diseases in Children that the results were “a little surprising.”

“There’s a small hint that for the cell-based H3N2 strain, there might be a little difference in microneutralization titers,” he said. “But otherwise, the comparisons did not meet statistical significance. We did not find any differences between the vaccines for hemagglutination inhibition for any strain of statistical significance.”

Zimmerman and colleagues noted that vaccines manufactured with egg tend to be more prone to mutation and could reduce the efficacy of the vaccine. For example, researchers said a mutation in egg-based A(H3N2) vaccine strains resulted in reduced vaccine efficacy during the 2016-2017 influenza season.

Child getting vaccinated 
Source: Shutterstock

Because of the reduced efficacy stemming from egg-based vaccines, manufacturers have shifted their focus to cell-based vaccines.

Results of a previously conducted study led by Seqirus found that a cell-based quadrivalent influenza vaccine was 36% more effective for patients aged 4 years and older compared with an egg-based vaccine.

“While egg-based vaccines are the standard of care and continue to play a critical role in the fight against influenza, real-world evidence has shown the potential for cell-based influenza vaccines to be more effective against certain influenza strains,” Jonathan M. Edelman, MD, vice president of clinical development at Seqirus, told Infectious Diseases in Children.

However, Zimmerman noted that because the study presented at IDWeek was an immunogenicity study rather than an efficacy study, the circulating virus would not have affected the results.

“We did this intentionally before widespread circulation of the virus, so that the wild virus would not mess up our results,” he said.

Zimmerman and colleagues randomly administered one of two FDA-approved influenza vaccines — one cell-based (n = 75) and one egg-based (n = 73) — to healthy patients aged 4 to 20 years. The researchers took blood samples before vaccination and 28 days after vaccination (range = 19 to 35 days) to test for hemagglutination inhibition (HAI) titers.

Demographic characteristics between the vaccine groups, including age, sex, race, ethnicity, parental education status, health insurance coverage and exposure to smoking in the household, were comparable, the researchers noted.

HAI response did not differ between children who received the cell-based vaccine and those who received the egg-based vaccine, but those who were unvaccinated in the previous season were more likely to seroconvert to any strain (68%) than those who were previously vaccinated (35%; P < .001).

“Those are substantial differences,” Zimmerman said. “We have a lot to learn about repeat vaccination.”

He added that the research team will conduct further analyses on the effect of prior influenza vaccination.

According to the researchers, the titer fold-rise difference 28 days after vaccination was 2 for influenza A(H1N1), 0.65 for influenza A(H3N2), 1.1 for influenza B(Colorado) and 0.9 for influenza B(Phuket).

“Because of the changing nature of the virus, studies that examine cases of influenza-like illness by vaccine type each season over a number of seasons are one of the best ways to understand the effectiveness of different types of influenza vaccine technologies in the real world,” Edelman said.

Zimmerman also noted the importance of conducting further research over the course of several years.

“I think we need more studies about cell-based vaccines,” he said. “One of the things you learn in the flu realm is that when you’ve seen one flu season, you’ve seen one flu season. Every season is different. To get a look at vaccines, you need at least 2 years so that you can take away some of these vagaries.” – by Katherine Bortz

References:

Boikos C, et al. Effectiveness of the cell culture- and egg-derived, seasonal influenza vaccine during the 2017-2018 Northern Hemisphere influenza season. Presented at: The National Foundation for Infectious Diseases Clinical Vaccinology Course; Nov. 9-10, 2018; Bethesda, Maryland.

Moehling K, et al. Abstract LB12. Presented at: IDWeek; Oct. 2-6, 2019; Washington.

Zost SJ, et al. Proc Natl Acad Sci. 2017;doi:10.1073/pnas.1712377114.

Disclosures: Edelman is an employee of Seqirus. Zimmerman reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.

Photo of Richard Zimmerman
Richard Zimmerman

WASHINGTON — Cell- and egg-based quadrivalent inactivated influenza vaccines have comparable immunogenicity for children aged 4 years and older, according to results from a randomized controlled trial presented at IDWeek.

Richard Zimmerman, MD, MPH, tenured professor of family medicine and clinical epidemiology at the University of Pittsburgh, told Infectious Diseases in Children that the results were “a little surprising.”

“There’s a small hint that for the cell-based H3N2 strain, there might be a little difference in microneutralization titers,” he said. “But otherwise, the comparisons did not meet statistical significance. We did not find any differences between the vaccines for hemagglutination inhibition for any strain of statistical significance.”

Zimmerman and colleagues noted that vaccines manufactured with egg tend to be more prone to mutation and could reduce the efficacy of the vaccine. For example, researchers said a mutation in egg-based A(H3N2) vaccine strains resulted in reduced vaccine efficacy during the 2016-2017 influenza season.

Child getting vaccinated 
Source: Shutterstock

Because of the reduced efficacy stemming from egg-based vaccines, manufacturers have shifted their focus to cell-based vaccines.

Results of a previously conducted study led by Seqirus found that a cell-based quadrivalent influenza vaccine was 36% more effective for patients aged 4 years and older compared with an egg-based vaccine.

“While egg-based vaccines are the standard of care and continue to play a critical role in the fight against influenza, real-world evidence has shown the potential for cell-based influenza vaccines to be more effective against certain influenza strains,” Jonathan M. Edelman, MD, vice president of clinical development at Seqirus, told Infectious Diseases in Children.

However, Zimmerman noted that because the study presented at IDWeek was an immunogenicity study rather than an efficacy study, the circulating virus would not have affected the results.

“We did this intentionally before widespread circulation of the virus, so that the wild virus would not mess up our results,” he said.

Zimmerman and colleagues randomly administered one of two FDA-approved influenza vaccines — one cell-based (n = 75) and one egg-based (n = 73) — to healthy patients aged 4 to 20 years. The researchers took blood samples before vaccination and 28 days after vaccination (range = 19 to 35 days) to test for hemagglutination inhibition (HAI) titers.

Demographic characteristics between the vaccine groups, including age, sex, race, ethnicity, parental education status, health insurance coverage and exposure to smoking in the household, were comparable, the researchers noted.

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HAI response did not differ between children who received the cell-based vaccine and those who received the egg-based vaccine, but those who were unvaccinated in the previous season were more likely to seroconvert to any strain (68%) than those who were previously vaccinated (35%; P < .001).

“Those are substantial differences,” Zimmerman said. “We have a lot to learn about repeat vaccination.”

He added that the research team will conduct further analyses on the effect of prior influenza vaccination.

According to the researchers, the titer fold-rise difference 28 days after vaccination was 2 for influenza A(H1N1), 0.65 for influenza A(H3N2), 1.1 for influenza B(Colorado) and 0.9 for influenza B(Phuket).

“Because of the changing nature of the virus, studies that examine cases of influenza-like illness by vaccine type each season over a number of seasons are one of the best ways to understand the effectiveness of different types of influenza vaccine technologies in the real world,” Edelman said.

Zimmerman also noted the importance of conducting further research over the course of several years.

“I think we need more studies about cell-based vaccines,” he said. “One of the things you learn in the flu realm is that when you’ve seen one flu season, you’ve seen one flu season. Every season is different. To get a look at vaccines, you need at least 2 years so that you can take away some of these vagaries.” – by Katherine Bortz

References:

Boikos C, et al. Effectiveness of the cell culture- and egg-derived, seasonal influenza vaccine during the 2017-2018 Northern Hemisphere influenza season. Presented at: The National Foundation for Infectious Diseases Clinical Vaccinology Course; Nov. 9-10, 2018; Bethesda, Maryland.

Moehling K, et al. Abstract LB12. Presented at: IDWeek; Oct. 2-6, 2019; Washington.

Zost SJ, et al. Proc Natl Acad Sci. 2017;doi:10.1073/pnas.1712377114.

Disclosures: Edelman is an employee of Seqirus. Zimmerman reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective
    Kathryn M. Edwards

    Kathryn M. Edwards

    At the recent IDWeek in Washington, D.C., investigators from the University of Pittsburgh compared immune responses to cell-based and egg-based quadrivalent inactivated influenza vaccines in children during the 2018-2019 influenza season. Healthy children aged 4 to 20 years were randomly assigned to the two vaccines in a 1:1 ratio. The immune responses were measured with standard HAI and were found to be comparable between the two vaccines for all four influenza strains included in the vaccines. The immune responses to vaccine were higher in those children who were not vaccinated in the previous season.

    In attempts to produce more immunogenic and protective vaccines, cell culture-grown vaccine strains have been produced to eliminate concerns that egg-grown vaccine viruses may lose protective epitopes that persist in cell culture-grown viruses. In this relatively small study that did not include measures of vaccine effectiveness, no differences were noted in immune responses.

    Additional comparisons of cell-grown and egg-grown vaccine viruses should be continued, but other methods to enhance immunogenicity should also be evaluated, such as the use of adjuvants.

    • Kathryn M. Edwards, MD
    • Infectious Diseases in Children Editorial Board member
      Sarah H. Sell and Cornelius Vanderbilt Chair in Pediatrics
      Professor of pediatrics
      Vanderbilt University Medical Center

    Disclosures: Edwards reports serving on data safety monitoring boards for Roche, Sanofi Pasteur and Seqirus, and advisory groups for Merck, Bionet, GlaxoSmithKline and X4 Pharmaceuticals.

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