Cell Culture-based Influenza Vaccines as Alternatives to Egg-based Vaccines

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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Safety and tolerability of cell culture-derived and egg-derived trivalent influenza vaccines in 3 to <18-year-old children and adolescents at risk of influenza-related complications

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2016.06.018 ◽

2016 ◽

Vol 49 ◽

pp. 171-178 ◽

Cited By ~ 3

Author(s):

Javier Diez-Domingo ◽

Maurizio de Martino ◽

Jose Garcia-Sicilia Lopez ◽

Gian Vincenzo Zuccotti ◽

Giancarlo Icardi ◽

...

Keyword(s):

At Risk ◽

Cell Culture ◽

Children And Adolescents ◽

Influenza Vaccines

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

Expert Review of Vaccines ◽

10.1586/erv.11.101 ◽

2011 ◽

Vol 10 (8) ◽

pp. 1127-1130 ◽

Cited By ~ 2

Author(s):

Christopher S Ambrose

Keyword(s):

Cell Culture ◽

Influenza Vaccines ◽

Younger Adults ◽

Correlates Of Protection

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Viral Subpopulation Screening Guides in Designing a High Interferon-Inducing Live Attenuated Influenza Vaccine by Targeting Rare Mutations in NS1 and PB2 Proteins

Journal of Virology ◽

10.1128/jvi.01722-20 ◽

2020 ◽

Vol 95 (2) ◽

pp. e01722-20

Author(s):

Amir Ghorbani ◽

Michael C. Abundo ◽

Hana Ji ◽

Kara J. M. Taylor ◽

John M. Ngunjiri ◽

...

Keyword(s):

Cell Culture ◽

Influenza Vaccine ◽

Influenza Viruses ◽

Translation Initiation Factor ◽

Influenza Vaccines ◽

Effective Control ◽

Live Vaccines ◽

Live Attenuated Influenza Vaccine ◽

Nonstructural Protein 1 ◽

Interferon Responses

ABSTRACTInfluenza A viruses continue to circulate among wild birds and poultry worldwide, posing constant pandemic threats to humans. Effective control of emerging influenza viruses requires new broadly protective vaccines. Live attenuated influenza vaccines with truncations in nonstructural protein 1 (NS1) have shown broad protective efficacies in birds and mammals, which correlate with the ability to induce elevated interferon responses in the vaccinated hosts. Given the extreme diversity of influenza virus populations, we asked if we could improve an NS1-truncated live attenuated influenza vaccine developed for poultry (PC4) by selecting viral subpopulations with enhanced interferon-inducing capacities. Here, we deconstructed a de novo population of PC4 through plaque isolation, created a large library of clones, and assessed their interferon-inducing phenotypes. While most of the clones displayed the parental interferon-inducing phenotype in cell culture, few clones showed enhanced interferon-inducing phenotypes in cell culture and chickens. The enhanced interferon-inducing phenotypes were linked to either a deletion in NS1 (NS1Δ76-86) or a substitution in polymerase basic 2 protein (PB2-D309N). The NS1Δ76-86 deletion disrupted the putative eukaryotic translation initiation factor 4GI-binding domain and promoted the synthesis of biologically active interferons. The PB2-D309N substitution enhanced the early transcription of interferon mRNA, revealing a novel role for the 309D residue in suppression of interferon responses. We combined these mutations to engineer a novel vaccine candidate that induced additive amounts of interferons and stimulated protective immunity in chickens. Therefore, viral subpopulation screening approaches can guide the design of live vaccines with strong immunostimulatory properties.IMPORTANCE Effectiveness of NS1-truncated live attenuated influenza vaccines relies heavily on their ability to induce elevated interferon responses in vaccinated hosts. Influenza viruses contain diverse particle subpopulations with distinct phenotypes. We show that live influenza vaccines can contain underappreciated subpopulations with enhanced interferon-inducing phenotypes. The genomic traits of such virus subpopulations can be used to further improve the efficacy of the current live vaccines.

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