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. 2024 May 2;11(5):ofae175.
doi: 10.1093/ofid/ofae175. eCollection 2024 May.

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

Alicia N Stein  1 , Carrie W Mills  2 , Ian McGovern  3 , Kimberly W McDermott  2 , Alex Dean  2 , Alina N Bogdanov  2 , Sheena G Sullivan  4   5 , Mendel D M Haag  6
Affiliations

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

Alicia N Stein et al. Open Forum Infect Dis. .

Abstract

Background: Influenza vaccine viruses grown in eggs may acquire egg-adaptive mutations that may reduce antigenic similarity between vaccine and circulating influenza viruses and decrease vaccine effectiveness. We compared cell- and egg-based quadrivalent influenza vaccines (QIVc and QIVe, respectively) for preventing test-confirmed influenza over 3 US influenza seasons (2017-2020).

Methods: Using a retrospective test-negative design, we estimated the relative vaccine effectiveness (rVE) of QIVc vs QIVe among individuals aged 4 to 64 years who had an acute respiratory or febrile illness and were tested for influenza in routine outpatient care. Exposure, outcome, and covariate data were obtained from electronic health records linked to pharmacy and medical claims. Season-specific rVE was estimated by comparing the odds of testing positive for influenza among QIVc vs QIVe recipients. Models were adjusted for age, sex, geographic region, influenza test date, and additional unbalanced covariates. A doubly robust approach was used combining inverse probability of treatment weights with multivariable regression.

Results: The study included 31 824, 33 388, and 34 398 patients in the 2017-2018, 2018-2019, and 2019-2020 seasons, respectively; ∼10% received QIVc and ∼90% received QIVe. QIVc demonstrated superior effectiveness vs QIVe in prevention of test-confirmed influenza: rVEs were 14.8% (95% CI, 7.0%-22.0%) in 2017-2018, 12.5% (95% CI, 4.7%-19.6%) in 2018-2019, and 10.0% (95% CI, 2.7%-16.7%) in 2019-2020.

Conclusions: This study demonstrated consistently superior effectiveness of QIVc vs QIVe in preventing test-confirmed influenza over 3 seasons characterized by different circulating viruses and degrees of egg adaptation.

Keywords: cell-based quadrivalent influenza vaccine; egg adaptation; influenza; influenza virus mismatch; relative vaccine effectiveness.

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Conflict of interest statement

Potential conflicts of interest. A. N. S., I. M., and M. D. M. H. are employees of CSL Seqirus. C. W. M., K. W. M., A. D., and A. N. B. are employees of Veradigm. S. G. S. reports receipt of consulting fees for CSL Seqirus, Pfizer, Moderna, and EvoHealth.

Figures

Figure 1.
Figure 1.
Study population selection for each season. ARFI, acute respiratory or febrile illness; EHR, electronic health record; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine.
Figure 2.
Figure 2.
Percentage of study populations tested for influenza within 7 days of a documented acute respiratory or febrile illness. From the influenza seasons of 2017–2018 (dotted line), 2018–2019 (dashed line), and 2019–2020 (solid line). Data from the final season were truncated to avoid confounding factors due to onset of the COVID-19 pandemic.
Figure 3.
Figure 3.
Covariate balance of control population before (squares) and after (dots) inverse probability of treatment weighting. Standardized mean difference (SMD) values ≤0.1 (dotted line) indicate a negligible difference.
Figure 4.
Figure 4.
Adjusted relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) vs egg-based quadrivalent influenza vaccine (QIVe) over 3 influenza seasons in a doubly robust analysis based on inverse probability of treatment weighting.
Figure 5.
Figure 5.
Sensitivity analyses of relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) vs egg-based quadrivalent influenza vaccine (QIVe) by (1) propensity to be tested for influenza, (2) seasonal peak period, (3) matched index week (ie, individuals tested for influenza during the same week of the calendar year), and (4) exclusion of antibody (Ab) and culture tests for influenza.
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References

    1. Centers for Disease Control and Prevention . Disease burden of flu. 2022. Available at: https://www.cdc.gov/flu/about/burden/index.html. Accessed 5 October 2023.
    1. Tokars JI, Olsen SJ, Reed C. Seasonal incidence of symptomatic influenza in the United States. Clin Infect Dis 2018; 66:1511–8. - PMC - PubMed
    1. de Courville C, Cadarette SM, Wissinger E, Alvarez FP. The economic burden of influenza among adults aged 18 to 64: a systematic literature review. Influenza Other Respir Viruses 2022; 16:376–85. - PMC - PubMed
    1. Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices—United States, 2020–21 influenza season. MMWR Recomm Rep 2020; 69:1–24. - PMC - PubMed
    1. Peck H, Laurie KL, Rockman S, et al. Enhanced isolation of influenza viruses in qualified cells improves the probability of well-matched vaccines. NPJ Vaccines 2021; 6:149. - PMC - PubMed