In-depth phylogenetic analysis of the hemagglutinin gene of influenza A(H3N2) viruses circulating during the 2016-2017 season revealed egg-adaptive mutations of vaccine strains

ABSTRACT

Objectives: The authors conducted an in-depth phylogenetic analysis of the hemagglutinin (HA) gene of A(H3N2) identified during the 2016–2017 season to compare the circulating strains with both the egg-derived and cell-derived 2016–2017 candidate vaccine virus (CVV).

Methods: 162 HA1 sequences of H3N2 viruses identified during the 2016–2017 season were phylogenetically analyzed and compared with egg-/cell-derived CVV. The predicted vaccine efficacy (pVE) of egg-/cell-derived CVV against field strains was quantified by P_epitope model.

Results: All H3N2 belonged to 3C.2a genetic clade, most (80.2%) to 3C.2a1 sub-clade. Several H3N2 variants circulated in the 2016–2017 season. HA sequences of field H3N2 strains displayed greater identity with cell-derived CVV than with egg-derived CVV. The amino acid substitutions in positions 160 and 194 identified in egg-derived CVV affected the pVE, which was lower for egg-derived CVV than for cell-derived CVV.

Conclusions: The results suggested that reduced vaccine effectiveness observed in 2016–2017 season was probably due to changes in the HA of vaccine strains acquired upon adaptation in eggs, which are the basis of most manufacturing systems currently used globally. Egg-free vaccine manufacturing systems would be advisable to improve the effectiveness of influenza vaccines.

KEYWORDS:

• Cell-derived vaccine
• egg-adaptive mutations
• egg-derived vaccine
• influenza A(H3N2) virus
• influenza vaccine
• virus evolution

Acknowledgments

The authors would like to thank Dr Paola Canepa for her fundamental help in nucleic acid extraction, PCR and sequencing.

Author contributions

D Panatto and E Pariani were involved in the conception and design of the study; C Galli, A Orsi, L Pellegrinelli, PL Lai, G Guarona and E Ebranati were involved in the analysis and interpretation of the data; D Panatto, E Pariani and C Galli were involved in the drafting of the paper; G Icardi was involved in revising it critically for intellectual content; all authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary Material

Supplemental data for this article can be accessed here.

Additional information

Funding

This project was made possible by an unconditional contribution by Seqirus srl, which had no role in any aspect of the study design, study implementation, data analysis or interpretation of the results.