Review of Analyses Estimating Relative Vaccine Effectiveness of Cell-Based Quadrivalent Influenza Vaccine in Three Consecutive US Influenza Seasons

Abstract

The adaptation of influenza seed viruses in egg culture can result in a variable antigenic vaccine match each season. The cell-based quadrivalent inactivated influenza vaccine (IIV4c) contains viruses grown in mammalian cell lines rather than eggs. IIV4c is not subject to egg-adaptive changes and therefore may offer improved protection relative to egg-based vaccines, depending on the degree of match with circulating influenza viruses. We summarize the relative vaccine effectiveness (rVE) of IIV4c versus egg-based quadrivalent influenza vaccines (IIV4e) to prevent influenza-related medical encounters (IRMEs) from three retrospective observational cohort studies conducted during the 2017-2018, 2018-2019, and 2019-2020 US influenza seasons using the same underlying electronic medical record dataset for all three seasons-with the addition of linked medical claims for the latter two seasons. We identified IRMEs using diagnostic codes specific to influenza disease (ICD J09*-J11*) from the records of over 10 million people. We estimated rVE using propensity score methods adjusting for age, sex, race, ethnicity, geographic location, week of vaccination, and health status. Subgroup analyses included specific age groups. IIV4c consistently had higher relative effectiveness than IIV4e across all seasons assessed, which were characterized by different dominant circulating strains and variable antigenic drift or egg adaptation.

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

Figure 1

National summary of influenza-positive specimens as reported by public health laboratories in the US to the CDC and absolute vaccine effectiveness (aVE) as estimated by the CDC [32,38,42,43]. Week 40 is the last week in September/first week in October and week 20 ends mid-May.

Figure 2

CDC-estimated burden of influenza (and 95% uncertainty interval) for the selected age groups (5–17, 18–49, 50–64, and ≥65 years) in season 2017–2018, 2018–2019, and 2019–2020 [37,40,41,44,45]. Left panel: rate of outpatient visits for influenza per 100,000. Right panel: rate of influenza hospitalizations per 100,000.

Figure 3

Relative vaccine effectiveness (rVE) of cell-based quadrivalent inactivated influenza vaccine (IIV4c) vs. egg-based quadrivalent inactivated influenza vaccine (IIV4e) during three influenza seasons between 2017 and 2020 in subjects ≥4 years of age and selected age subgroups [22,23,25,26]. Point estimates are color coded based on the season of the study indicated on the left side of the table. CI, confidence interval.

Figure 4

Relative vaccine effectiveness (rVE) of cell-based quadrivalent inactivated influenza vaccine (IIV4c) vs. egg-based quadrivalent inactivated influenza vaccine (IIV4e) during periods of peak influenza activity overall and in age subgroups for seasons 2018–2019 and 2019–2020 [23,25,26]. Point estimates are color coded based on the season of the study indicated on the left side of the table. CI, confidence interval.