Cell-Based Quadrivalent Influenza Vaccine Displays Superiority Over 3 Flu Seasons

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A study of the flu seasons from 2017 to 2020 suggest that cell-based influenza vaccines outperformed egg-based vaccines in effectiveness.

Alicia N. Sein, PhD

(Credit: LnkedIn)

Alicia N. Sein, PhD

(Credit: LnkedIn)

The findings of a recent comparison of cell- and egg-based quadrivalent influenza vaccines for the prevention of test-confirmed influenza across the influenza seasons of 2017 to 2020 in the United States suggest that the cell-based vaccine demonstrated superior effectiveness, reporting a range of relative vaccine effectiveness (rVE) of roughly 10% to 15% across those seasons.1

The work, conducted by Alicia N. Stein, PhD, the director of Real World Evidence in the Centre for Outcomes Research and Epidemiology at CSL Seqirus, and colleagues, included study populations of 31,824 in the 2017–2018 season; 33,388 in the 2018–2019 season; and 34,398 in the 2019–2020 season. Of these, 3115 (9.8%), 3426 (10.3%), and 3890 (11.3%) were vaccinated with cell-based (accounting for ~10% of the total population) and 28,709 (90.2%), 29 962 (89.7%), and 30 508 (88.7%) with egg-based (accounting for ~90% of the total population), respectively.

All told, the respective rVE rates for 2017–2018, 2018–2019, and 2019–2020 were 14.8% (95% CI, 7.0-22.0), 12.5% (95% CI, 4.7-19.6), and 10.0% (95% CI, 2.7-16.7). Stein et al wrote that effectiveness “observed in this study is consistent with the expected advantages of propagation of human influenza viruses in qualified mammalian cell lines, obviating the need for egg-adapted mutations and doubling the rate of virus isolation as compared with egg-based propagation, thus improving the choice, match, and potentially the effectiveness of seasonal influenza vaccines as compared with egg-based vaccines.”1

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Existing literature suggest that egg-adaptive mutations can reduce antigenic similarity between vaccine and circulating influenza viruses, thus decreasing egg-based vaccine effectiveness. Stein said in a statement that the “study exemplifies the value of [real-world evidence] in generating valuable insights into the effectiveness of influenza vaccines."

The study, published in Open Forum Infectious Diseases, utilized a retrospectives test-negative design and included individuals aged 4 to 64 years with an acute respiratory or febrile illness (ARFI) and who were tested for influenza in routine outpatient care. Season-specific rVE was estimated by comparing the odds of a positive test for influenza between the 2 groups.

Stein and colleagues acknowledge that the work is subject to the limitations often associated with retrospective cohort analyses, including selection bias and residual confounding potentials. And, although a test-negative design offers advantages over other forms of assessment, the causality findings it produces are not as definitive as randomized controlled trials. In a news release, CSL Seqirus noted a recommendation for “interpreting these results within a comprehensive evidence framework that includes various study designs for a well-rounded perspective on vaccine efficacy/effectiveness.”

As for strengths of the work, the study’s population size and depth of patient information were helpful, according to the authors. Additionally, by limiting the sample to individual with an ARFI diagnosis within 7 days of an influenza test—which Stein and colleagues noted is “an indication that the test was performed because of the influenza-like symptoms”—it resulted in a more clinically homogeneous study population. Another strength noted by the authors was the focus on test-confirmed outcomes rather than clinical diagnoses of influenza, which may or may not have been informed by an influenza test.

"Cell-based technology allows us to provide an exact antigenic match to the WHO's identified strains, helping to improve vaccine effectiveness versus standard egg-based vaccines. These data build on the growing evidence of real-world data that shows the benefits of our cell-based influenza vaccine," Gregg Sylvester, MD, MPH, the Chief Health Officer and head of Medical Affairs at CSL Seqirus, said in a statement.2 "At CSL Seqirus, we're continually driving vaccine technology forward, in order to improve effectiveness and help keep communities healthy."

REFERENCES
1. Stein AN, Mills CW, MoGovern I, et al. Relative Vaccine Effectiveness of Cell- vs Egg-Based Quadrivalent Influenza Vaccine Against Test-Confirmed Influenza Over 3 Seasons Between 2017 and 2020 in the United States. Open Forum Infect Dis. 2024;11(5):ofae175. doi:10.1093/ofid/ofae175
2. Recently Published Real-World Evidence Study Shows Effectiveness of Cell-Based Quadrivalent Influenza Vaccine Over Three Seasons. News release. CSL Seqirus. May 2, 2024. Accessed May 17, 2024. https://prnmedia.prnewswire.com/news-releases/recently-published-real-world-evidence-study-shows-effectiveness-of-cell-based-quadrivalent-influenza-vaccine-over-three-seasons-302134540.html
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