Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016

Bolton, Marcus J.; Abente, Eugenio J.; Venkatesh, Divya; Stratton, Jered A.; Zeller, Michael A.; Anderson, Tavis K.; Lewis, Nicola S.; Vincent, Amy L.

doi:10.1111/irv.12610

Cited by 29 publications

(33 citation statements)

References 25 publications

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“…WIV and RP can also be formulated with autogenous or custom farm-based strains. The production of "off-the-shelf" commercially available efficacious WIV vaccines is difficult because of the number of strains in the vaccine required to immunize against all antigenically distinct circulating IAV strains in swine (Rajao et al 2018a;Bolton et al 2019). Formulating effective vaccines is further challenged by the difficulty in updating vaccine seed viruses given the emergence of novel lineages, antigenic drift, the time needed to approve and license veterinary vaccine products, maternal antibody interference, and the lack of adequate mucosal and cell-mediated immune responses (Kitikoon et al 2006;Wesley and Lager 2006;Platt et al 2011).…”

Section: N2 Geographic Origin Of Swine Influenzamentioning

confidence: 99%

Swine Influenza A Viruses and the Tangled Relationship with Humans

Anderson

Chang

Arendsee

et al. 2020

Cold Spring Harb Perspect Med

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127

122

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Influenza A viruses (IAVs) are the causative agents of one of the most important viral respiratory diseases in pigs and humans. Human and swine IAV are prone to interspecies transmission, leading to regular incursions from human to pig and vice versa. This bidirectional transmission of IAV has heavily influenced the evolutionary history of IAV in both species. Transmission of distinct human seasonal lineages to pigs, followed by sustained within-host transmission and rapid adaptation and evolution, represent a considerable challenge for pig health and production. Consequently, although only subtypes of H1N1, H1N2, and H3N2 are endemic in swine around the world, extensive diversity can be found in the hemagglutinin (HA) and neuraminidase (NA) genes, as well as the remaining six genes. We review the complicated global epidemiology of IAV in swine and the inextricably entangled implications for public health and influenza pandemic planning.

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Section: N2 Geographic Origin Of Swine Influenzamentioning

confidence: 99%

Swine Influenza A Viruses and the Tangled Relationship with Humans

Anderson

Chang

Arendsee

et al. 2020

Cold Spring Harb Perspect Med

Self Cite

127

122

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“…The possible impact that herd level persistence of IAV might have on antigenic drift over time in a specific population of pigs, has, to the best of our knowledge, never been investigated. However, we believe it is highly important to get an increased understanding of antigenic drift occurring within single herds, as it can help explain the high genetic diversity within swIAV lineages documented in large-scale investigations and surveillance programs [25][26][27]29,48,49]. Importantly, if positive selection comparable to that observed in human IAV occurs in swine IAV, the possible effects on herd immunity and vaccination, should be taken into consideration when designing vaccines and evaluating swIAV control programs.…”

Section: Introductionmentioning

confidence: 99%

Substantial Antigenic Drift in the Hemagglutinin Protein of Swine Influenza A Viruses

Ryt-Hansen

Pedersen

Larsen

et al. 2020

Viruses

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The degree of antigenic drift in swine influenza A viruses (swIAV) has historically been regarded as minimal compared to that of human influenza A virus strains. However, as surveillance activities on swIAV have increased, more isolates have been characterized, revealing a high level of genetic and antigenic differences even within the same swIAV lineage. The objective of this study was to investigate the level of genetic drift in one enzootically infected swine herd over one year. Nasal swabs were collected monthly from sows (n = 4) and piglets (n = 40) in the farrowing unit, and from weaners (n = 20) in the nursery. Virus from 1–4 animals were sequenced per month. Analyses of the sequences revealed that the hemagglutinin (HA) gene was the main target for genetic drift with a substitution rate of 7.6 × 10−3 substitutions/site/year and evidence of positive selection. The majority of the mutations occurred in the globular head of the HA protein and in antigenic sites. The phylogenetic tree of the HA sequences displayed a pectinate typology, where only a single lineage persists and forms the ancestor for subsequent lineages. This was most likely caused by repeated selection of a single immune-escape variant, which subsequently became the founder of the next wave of infections.

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“…This effort is fraught with risk as there are at least 16 distinct HA genetic clades of IAV in swine derived from multiple human-to-swine interspecies transmission events and subsequent evolution in the swine host (8,11). Further, there is evidence for regional patterns in HA clade persistence (8,12), and the demonstration that as few as six amino acid mutations within the HA may affect the antigenic phenotype of a virus (13,14). Consequently, there is a critical need to not only sequence and genetically characterize swine IAV, but determine what of the genetic diversity is meaningful for antigenic drift.…”

Section: Introductionmentioning

confidence: 99%

“…Structural changes in the HA may alter the interaction with antibodies targeting the virus, and these changes are generally correlated with the number of accumulated amino acid mutations in the HA protein (19). Empirical data has also shown that certain amino acid mutations have a disproportionate effect on antigenic change based on the location of the amino acid in the protein structure (13,15). Though there are relatively few antigenically characterized swine IAV HA genes (9,13), this empirical data may be used to establish antigenic distances between multiple IAV in swine, and be used to gain insight on the contribution of site-specific amino acid mutations.…”

Section: Introductionmentioning

confidence: 99%

“…Empirical data has also shown that certain amino acid mutations have a disproportionate effect on antigenic change based on the location of the amino acid in the protein structure (13,15). Though there are relatively few antigenically characterized swine IAV HA genes (9,13), this empirical data may be used to establish antigenic distances between multiple IAV in swine, and be used to gain insight on the contribution of site-specific amino acid mutations. These data can subsequently be used to assign a level of importance to specific amino acid mutations and be used to predict antigenic drift and the biological relevance of genetic diversity collected during surveillance programs.…”

Section: Introductionmentioning

confidence: 99%

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Machine learning prediction and experimental validation of antigenic drift in H3 influenza A viruses in swine

Zeller

Gauger

Arendsee

et al. 2020

Preprint

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The antigenic diversity of influenza A virus (IAV) circulating in swine challenges the development of effective vaccines, increasing zoonotic threat and pandemic potential. High throughput sequencing technologies are able to quantify IAV genetic diversity, but there are no accurate approaches to adequately describe antigenic phenotypes. This study evaluated an ensemble of non-linear regression models to estimate virus phenotype from genotype. Regression models were trained with a phenotypic dataset of pairwise hemagglutination inhibition (HI) assays, using genetic sequence identity and pairwise amino acid mutations as predictor features. The model identified amino acid identity, ranked the relative importance of mutations in the hemagglutinin (HA) protein, and demonstrated good prediction accuracy. Four previously untested IAV strains were selected to experimentally validate model predictions by HI assays. Error between predicted and measured distances of uncharacterized strains were 0.34, 0.70, 2.19, and 0.17 antigenic units. These empirically trained regression models can be used to estimate antigenic distances between different strains of IAV in swine using sequence data. By ranking the importance of mutations in the HA, we provide criteria for identifying antigenically advanced IAV strains that may not be controlled by existing vaccines and can inform strain updates to vaccines to better control this pathogen.

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Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016

Cited by 29 publications

References 25 publications

Swine Influenza A Viruses and the Tangled Relationship with Humans

Swine Influenza A Viruses and the Tangled Relationship with Humans

Substantial Antigenic Drift in the Hemagglutinin Protein of Swine Influenza A Viruses

Machine learning prediction and experimental validation of antigenic drift in H3 influenza A viruses in swine

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