Efficacy and correlates of protection for cell culture-derived and egg-derived inactivated influenza vaccines in younger adults

Abstract Background 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. Methods 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. Results 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%). Conclusions 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.

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Influenza Vaccines – Challenges in Mammalian Cell Culture Technology

Cell Technology for Cell Products ◽

10.1007/978-1-4020-5476-1_85 ◽

2007 ◽

pp. 503-508 ◽

Cited By ~ 2

Author(s):

Yvonne Genzel ◽

Josef Schulze-Horsel ◽

Lars Möhler ◽

Yury Sidorenko ◽

Udo Reichl

Keyword(s):

Cell Culture ◽

Mammalian Cell ◽

Mammalian Cell Culture ◽

Influenza Vaccines ◽

Culture Technology

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Cell Culture-Derived Influenza Vaccines

Influenza Vaccines for the Future ◽

10.1007/978-3-0346-0279-2_12 ◽

2010 ◽

pp. 293-312 ◽

Cited By ~ 4

Author(s):

Philip R. Dormitzer

Keyword(s):

Cell Culture ◽

Influenza Vaccines

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Distinguishing Causation from Correlation in the Use of Correlates of Protection to Evaluate and Develop Influenza Vaccines

American Journal of Epidemiology ◽

10.1093/aje/kwz227 ◽

2019 ◽

Vol 189 (3) ◽

pp. 185-192 ◽

Cited By ~ 1

Author(s):

Wey Wen Lim ◽

Nancy H L Leung ◽

Sheena G Sullivan ◽

Eric J Tchetgen Tchetgen ◽

Benjamin J Cowling

Keyword(s):

Vaccine Efficacy ◽

Vaccine Development ◽

Influenza Vaccines ◽

Protective Effects ◽

Immune Markers ◽

Immune Marker ◽

Correlates Of Protection ◽

Rational Vaccine Design ◽

Individual Protection ◽

Protection Against Infection

Abstract There is increasing attention to the need to identify new immune markers for the evaluation of existing and new influenza vaccines. Immune markers that could predict individual protection against infection and disease, commonly called correlates of protection (CoPs), play an important role in vaccine development and licensing. Here, we discuss the epidemiologic considerations when evaluating immune markers as potential CoPs for influenza vaccines and emphasize the distinction between correlation and causation. While an immune marker that correlates well with protection from infection can be used as a predictor of vaccine efficacy, it should be distinguished from an immune marker that plays a mechanistic role in conferring protection against a clinical endpoint—the latter might be a more reliable predictor of vaccine efficacy and a more appropriate target for rational vaccine design. To clearly distinguish mechanistic and nonmechanistic CoPs, we suggest using the term “correlates of protection” for nonmechanistic CoPs, and ‘‘mediators of protection’’ for mechanistic CoPs. Furthermore, because the interactions among and relative importance of correlates or mediators of protection can vary according to age or prior vaccine experience, the effect sizes and thresholds for protective effects for CoPs could also vary in different segments of the population.

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