Cell-cultured quadrivalent influenza vaccines may have greater effectiveness compared with standard, egg-derived quadrivalent influenza vaccines, according to results of a study published in Clinical Infectious Diseases.

Since 2010, influenza has resulted in an estimated 9.2 to 60.8 million cases, 140,000 to 710,000 hospitalization, and 12,000 to 56,000 deaths annually in the United States. Influenza vaccines include the expected circulating strains for each year. The most contemporary influenza virus vaccines are produced from viruses grown in embryonated chicken eggs; however, in response to selective pressures in the eggs, influenza viral antigens may undergo adaptive mutations and reduce vaccine effectiveness. During the 2017 to 2018 influenza season, the estimated interim vaccine effectiveness was 40%, and the lowest strain-specific effectiveness was 24%, which was the dominant A (H3N2) strain that season.

Alternatively, during the 2017 to 2018 influenza season, a quadrivalent ccIIV vaccine was produced using an A (H3N2) virus propagated exclusively in cell culture using mammalian cells; therefore, this vaccine lacked egg adaptive changes and improved the match between the vaccine virus strain and the vaccine selective strain, potentially improving vaccine effectiveness. Although some comparative effectiveness studies have been performed, more data is needed to elucidate the benefits of ccIIV4 vaccination. Therefore, this retrospective cohort study estimated the relative vaccine effectiveness of ccIIV4 vs egg-derived quadrivalent vaccines (egg-derived IIV4) in 2017 to 2018 in the United States.

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In total, 1,353,862 individuals (aged ³ 4 years) received seasonal vaccinations and were included in the study. Primary care electronic medical records were used to retrospectively collect vaccination, outcome, and covariate data. The influenza-like illnesses recorded within primary care practice was the evaluated outcome, which was defined by the presence of specific diagnostic codes in the subject primary care electronic medical record database. Relative vaccine effectiveness was estimated against influenza-like illness using diagnostic ICD-9 and ICD-10 codes. Multivariable logistic regression models that were adjusted for age, sex, race, ethnicity, geographic region, and health status were used to estimate adjusted odds rations and derive relative vaccine effectiveness estimates.

Data suggested that the ccIIV4 vaccine may have greater effectiveness compared with the egg-derived vaccine. Of the included cases, 92,187 (6.8%) individuals received ccIIV4 and 1,261,675 (93%) individuals received egg-derived IIV4. Of all the vaccinations included, 55% were received by individuals who were between age 18 and 64 years; however, prior to adjustment, patients in the ccIIV4 exposure group were older than those in the egg-derived IIV4 group (median age of 59 vs 42 years, respectively). In total, 27,350 (2.0%) influenza-like illnesses events occurred: 1705 (1.88%) influenza-like illnesses events in the ccIIV4 group and 25,645 (2.07%) events occurred in the egg-derived IIV4 group.

The incidence of influenza-like illnesses events was highest in youngest children and declined steadily as age increased up to age 18 years. Defined influenza-like illnesses events occurred 1,705 times in the ccIIV4 group and 25, 645 times in the standard egg-derived IIV4 group. Before adjustment, the estimated crude relative vaccine effectiveness was 9.2% (95% CI, 4.6%-13.6%). After adjustment for age, sex, health, status, and geographic region, the estimated relative vaccine effectiveness was 36.2% (95% CI, 26.1%-44.9%; P <.001).

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Although vaccine effectiveness depends on factors including those at the individual level, vaccine level, and virus level, overall, the study authors conclude that, “The productive of vaccines using cell-propagated influenza viruses eliminates opportunities for viral mutations to occur and maintains viral antigenicity, which supports improved effectiveness of ccIIV4 observed in this study.”


Boikos C, Sylvester GC, Sampalis JS, Mansi JA. Relative effectiveness of the cell-cultured quadrivalent influenza vaccine compared to standard, egg-derived quadrivalent influenza vaccines in preventing influenza-like illness in 2017-2018 [published online April 7, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa371/5816768