Abstract

The trivalent seasonal influenza vaccine was the only approved and available vaccine during the 2016–2018 influenza seasons. It did not include the B/Yamagata strain. In this study, we report an acute respiratory disease outbreak associated with influenza B/Yamagata infections in Guangzhou, Southern China (January through March, 2018). Among the 9914 patients, 2241 (22.6%) were positive for the influenza B virus, with only 312 (3.1%) positive for the influenza A virus. The influenza B/Yamagata lineage dominated during this period in Southern China. The highest incidence of influenza A virus infection occurred in the children aged 5–14 years. In contrast, populations across all age groups were susceptible to the influenza B virus. Phylogenetic, mutations, and 3D structure analyses of hemagglutinin (HA) genes were performed to assess the vaccine-virus relatedness. The recommended A/H1N1 vaccine strain (A/Michigan/45/2015) during both 2017–2018 and 2018–2019 was antigen-specific for these circulating isolates (clade 6B.1) in Spring 2018. An outbreak of influenza B/Yamagata (clade 3) infections in 2018 occurred during the absence of the corresponding vaccine during 2016–2018. The recommended influenza B/Yamagata vaccine strain (B/Phuket/3073/2013) for the following season (2018–2019) was antigen-specific. Although there were only a few influenza B/Victoria infections in Spring 2018, five amino acid mutations were identified in the HA antigenic sites of the 19 B/Victoria isolates (clade 1A), when compared with the 2016–2018 B/Victoria vaccine strain. The number was larger than expected and suggested that the influenza B HA gene may be more variable than previously thought. One of the mutations (K180N) was noted to likely alter the epitope and to potentially affect the viral antigenicity. Seven mutations were also identified in the HA antigenic sites of 2018–2020 B/Victoria vaccine strain, of which some or all may reduce immunogenicity and the protective efficacy of the vaccine, perhaps leading to more outbreaks in subsequent seasons. The combined epidemiological, phylogenetic, mutations, and 3D structural analyses of the HA genes of influenza strains reported here contribute to the understanding and evaluation of how HA mutations affect vaccine efficacy, as well as to providing important data for screening and selecting more specific, appropriate, and effective influenza vaccine candidate strains.

Highlights

  • Influenza viruses are the major cause of acute respiratory diseases in humans, causing several serious global pandemics because of their transmission dynamics and great antigenic variability

  • Pandemic influenza is usually caused by influenza A virus, due to its rapid antigenic variation, strong replication capacity, and transmission ability associated with genetic reassortment (Chan et al, 2010; White and Lowen, 2018)

  • The sequence data resulted in the typing of the influenza A strains as 23 H1N1 with one H3N2, and the typing of influenza B as identified 80 Yamagata and 19 Victoria strains

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Summary

Introduction

Influenza viruses are the major cause of acute respiratory diseases in humans, causing several serious global pandemics because of their transmission dynamics and great antigenic variability. Compounding this is the potential of emergent strains originating in swine and avian hosts (Mostafa et al, 2018), as well as from reverse zoonosis from human to animals (Morens et al, 2013; Nelson and Vincent, 2015). Influenza B virus, including the Victoria and Yamagata lineages, is hosted by humans and seals (Osterhaus et al, 2000). In the 2016–2018 seasons, the trivalent influenza vaccine did not include the B/Yamagata lineage

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