Influenza antigens may undergo adaptive mutations during egg-based vaccine production. In the 2017–2018 influenza season, quadrivalent, inactivated cell-derived influenza vaccine (ccIIV4) vaccine was produced using A(H3N2) seed virus propagated exclusively in cell culture, thus lacking egg adaptive changes. This United States study estimated relative vaccine effectiveness (rVE) of ccIIV4 vs egg-derived quadrivalent vaccines (egg-derived IIV4) for that season. Vaccination, outcome, and covariate data were ascertained retrospectively from a electronic medical record (EMR) dataset and analyzed. The study cohort included patients ≥ 4 years of age. rVE was estimated against influenza-like illness (ILI) using diagnostic International Classification of Diseases, Ninth or Tenth Revision codes. The adjusted odds ratios used to derive rVE estimates were estimated from multivariable logistic regression models adjusted for age, sex, race/ethnicity, geographic region, and health status. Overall, 92 187 individuals had a primary care EMR record of ccIIV4 and 1 261 675 had a record of egg-derived IIV4. In the ccIIV4 group, 1705 narrowly defined ILI events occurred, and 25 645 occurred in the standard egg-derived IIV4 group. Crude rVE was 9.2% (95% confidence interval [CI], 4.6%–13.6%). When adjusted for age, sex, health status, comorbidities, and geographic region, the estimated rVE changed to 36.2% (95% CI, 26.1%–44.9%). ccIIV4, derived from A(H3N2) seed virus propagated exclusively in cell culture, was more effective than egg-derived IIV4 in preventing ILI during the 2017–2018 influenza season. This result suggests that cell-derived influenza vaccines may have greater effectiveness than standard egg-derived vaccines.

The effectiveness of standard, egg-derived quadrivalent influenza vaccines (IIV4) may be reduced in adults ≥65 years of age, largely because of immunosenescence. An MF59-adjuvanted trivalent influenza vaccine (aIIV3) and a high-dose trivalent influenza vaccine (HD-IIV3) offer older adults enhanced protection versus standard vaccines. This study compared the relative effectiveness of aIIV3 with IIV4 and HD-IIV3 in preventing influenza-related medical encounters over 2 US influenza seasons. This retrospective cohort study included US patients ≥65 years vaccinated with aIIV3, IIV4, or HD-IIV3. The outcome of interest was the occurrence of influenza-related medical encounters. Data were derived from a large dataset comprising primary and specialty care electronic medical records linked with pharmacy and medical claims. Adjusted odds ratios (OR) were derived from an inverse probability of treatment-weighted sample adjusted for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness (rVE) was determined using the formula (% VE = 1 – OR_adjusted) × 100. In 2017–2018, cohorts included: aIIV3, n = 524 223; IIV4, n = 917 609; and HD-IIV3, n = 3 377 860. After adjustment, 2017–2018 rVE of aIIV3 versus IIV4 was 18.2 (95% confidence interval [CI], 15.8–20.5); aIIV3 vs. HD-IIV3 was 7.7 (95% CI, 2.3–12.8). In 2018–2019, cohorts included: aIIV3, n = 1 031 145; IIV4, n = 915 380; HD-IIV3, n = 3 809 601, with adjusted rVEs of aIIV3 versus IIV4 of 27.8 (95% CI, 25.7–29.9) and vs. HD-IIV3 of 6.9 (95% CI, 3.1–10.6). In the 2017–2018 and 2018–2019 influenza seasons in the United States, aIIV3 demonstrated greater reduction in influenza-related medical encounters than IIV4 and HD-IIV3 in adults ≥65 years.

Background: The cell-propagated inactivated quadrivalent influenza vaccine (ccIIV4) may offer improved protection in seasons where egg-derived influenza viruses undergo mutations that affect antigenicity. This study estimated the relative vaccine effectiveness (rVE) of ccIIV4 versus egg-derived inactivated quadrivalent influenza vaccine (eIIV4) in preventing influenza-related medical encounters in the 2018–2019 US season. Methods: A dataset linking primary care electronic medical records with medical claims data was used to conduct a retrospective cohort study among individuals ≥ 4 years old vaccinated with ccIIV4 or eIIV4 during the 2018–2019 season. Adjusted odds ratios (ORs) were derived from a doubly robust inverse probability of treatment-weighted approach adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. rVE was estimated by (1 – OR) × 100 and presented with 95% confidence intervals (CI). Results: Following the application of inclusion/exclusion criteria, the study cohort included 2 125 430 ccIIV4 and 8 000 903 eIIV4 recipients. Adjusted analyses demonstrated a greater reduction in influenza-related medical encounters with ccIIV4 versus eIIV4, with the following rVE: overall, 7.6% (95% CI, 6.5–8.6); age 4–17 years, 3.9% (95% CI, .9–7.0); 18–64 years, 6.5% (95% CI, 5.2–7.9); 18–49 years, 7.5% (95% CI, 5.7–9.3); 50–64 years, 5.6% (95% CI, 3.6–7.6); and ≥65 years, –2.2% (95% CI, –5.4 to .9). Conclusions: Adjusted analyses demonstrated statistically significantly greater reduction in influenza-related medical encounters in individuals vaccinated with ccIIV4 versus eIIV4 in the 2018–2019 US influenza season. These results support ccIIV4 as a potentially more effective public health measure against influenza than an egg-based equivalent.

Real-world evidence (RWE) increasingly informs public health and healthcare decisions worldwide. A large database has been created (“Integrated Dataset”) that integrates primary care electronic medical records with pharmacy and medical claims data on >123 million US patients since 2014. This article describes the components of the Integrated Dataset and evaluates its representativeness to the US population and its potential use in evaluating influenza vaccine effectiveness. Representativeness to the US population (2014–2019) was evaluated by comparison with demographic information from the 2019 US census and the National Ambulatory Medical Care Survey (NAMCS). Variables included in the Integrated Dataset were evaluated against World Health Organization (WHO) defined key and non-critical variables for evaluating influenza vaccine performance. The Integrated Dataset contains a variety of information, including demographic data, patient medical history, diagnoses, immunizations, and prescriptions. Distributions of most age categories and sex were comparable with the US Census and NAMCS populations. The Integrated Dataset was less diverse by race and ethnicity. Additionally, WHO key and non-critical variables for the estimation of influenza vaccine effectiveness are available in the Integrated Dataset. In summary, the Integrated Dataset is generally representative of the US population and contains key variables for the assessment of influenza vaccine effectiveness.

Background: Egg-based influenza vaccine production can lead to the accumulation of mutations that affect antigenicity. The mammalian cell-based inactivated quadrivalent influenza vaccine (IIV4c) may improve effectiveness compared with egg-based vaccines. This study estimated the relative vaccine effectiveness (rVE) of IIV4c versus egg-based inactivated quadrivalent influenza vaccine (IIV4e) in preventing influenza-related medical encounters (IRME) among children and adolescents during the 2019–2020 US influenza season. Methods: This retrospective cohort study used a dataset linking primary and specialty care electronic medical records with medical and pharmacy claims data from US residents 4 through 17 years of age vaccinated with IIV4c or IIV4e during the 2019–2020 influenza season. Odds ratios (ORs) were derived from a doubly robust inverse probability of treatment-weighted approach adjusting for age, sex, race, ethnicity, region, index week, health status and two proxy variables for healthcare accessibility and use. Adjusted rVE was estimated by (1-OR_adjusted)*100, and an exploratory analysis evaluated IRMEs separately for outpatient and inpatient settings. Results: The final study cohort included 60,480 (IIV4c) and 1,240,990 (IIV4e) vaccine recipients. Fewer IRMEs were reported in subjects vaccinated with IIV4c than IIV4e. The rVE for IIV4c versus IIV4e was 12.2% [95% confidence interval (CI): 7.5–16.6] for any IRME and 14.3% (9.3–19.0) for outpatient IRMEs. Inpatient IRMEs were much less frequent, and effectiveness estimates were around the null. Conclusions: Fewer IRMEs occurred in pediatric subjects vaccinated with IIV4c versus IIV4e. These results support the greater effectiveness of IIV4c over IIV4e in this population during the 2019–2020 US influenza season.

MF59^®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose trivalent inactivated influenza vaccine (HD-IIV3) elicit an enhanced immune response in older adults compared to standard, quadrivalent inactivated influenza vaccines (IIV4). We sought to determine the relative vaccine effectiveness (rVE) of aIIV3 versus IIV4 and HD-IIV3 in preventing influenza-related medical encounters in this retrospective cohort study involving adults ≥65 years with ≥1 health condition during the 2017–2018 and 2018–2019 influenza seasons. Data were obtained from primary and specialty care electronic medical records linked with pharmacy and medical claims. Adjusted odds ratios (OR) were derived from an inverse probability of treatment-weighted sample adjusted for age, sex, race, ethnicity, geographic region, vaccination week, and health status. rVE was determined using the formula (% rVE = 1 − OR_adjusted) × 100. Analysis sets included 1,755,420 individuals for the 2017–2018 season and 2,055,012 for the 2018–2019 season. Compared to IIV4, aIIV3 was 7.1% (95% confidence interval 3.3–10.8) and 20.4% (16.2–24.4) more effective at preventing influenza-related medical encounters in the 2017–2018 and 2018–2019 seasons, respectively. Comparable effectiveness was observed with HD-IIV3 across both seasons. Our results support improved effectiveness of aIIV3 vs IIV4 in a vulnerable population of older adults at high risk of influenza and its complications.