Background: Estimates of annual effectiveness of influenza vaccination combine multiple vaccine types. Reports of brand/product-specific vaccine effectiveness (VE) of egg- and cell-culture based quadrivalent inactivated influenza vaccines (IIV4/ccIIV4) are limited.

Methods: Using an observational test-negative study design, we compared effectiveness of selected IIV4 and ccIIV4 products among outpatients enrolled in the US Flu VE Network from 2014-2015 to 2018-2019. We used multivariable logistic regression to estimate product- and age-group-specific absolute and relative effectiveness of recommended, age-appropriate vaccines against symptomatic laboratory-confirmed outpatient influenza. Relative effectiveness of ccIIV4 versus IIV4 products was estimated during two seasons from 2017-2019 among participants aged ≥4 years.

Results: Pooling data from five influenza seasons when 18% and 15% of vaccinated patients had received Fluarix? Quadrivalent or Fluzone? Quadrivalent IIV4, respectively, VE against influenza was 32% for Fluarix IIV4 and 37% for Fluzone IIV4. Pooling two seasons when 11% and 28% of vaccinated patients had received ccIIV4/Flucelvax? Quadrivalent and FluLaval? Quadrivalent IIV4, respectively, VE against influenza for each product was 30%. Absolute VE compared to unvaccinated patients was lowest against influenza A(H3N2) compared to that against A(H1N1)pdm09 and each B lineage; VE point estimates were lowest among patients aged ≥50 years compared to two younger age-groups. Relative effectiveness estimates were not statistically significant, indicating similar protection across vaccine products.

Conclusion: Comparisons of influenza vaccine products over multiple seasons showed benefit against symptomatic laboratory-confirmed outpatient influenza of both egg- and cell culture-based quadrivalent inactivated influenza vaccines, with similar absolute and relative levels of protection provided by each product.