Diagnostic detection of live attenuated influenza virus vaccine virus and evidence of reassortment in United States swine

Authors: SHARMA, ADITI - Iowa State University; ZELLER, MICHAEL - Iowa State University; LI, GANWU - Iowa State University; HARMON, KAREN - Iowa State University; ZHANG, JIANQIANG - Iowa State University; HOANG, HAI - Nong Lam University; Anderson, Tavis; Baker, Amy; GAUGER, PHILLIP - Iowa State University

Submitted to: Journal of Veterinary Diagnostic Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2019
Publication Date: 2/26/2020
Citation: Sharma, A., Zeller, M.A., Li, G., Harmon, K., Zhang, J., Hoang, H., Anderson, T.K., Vincent, A.L., Gauger, P.C. 2020. Detection of live attenuated influenza vaccine virus and evidence of reassortment in U.S. swine population. Journal of Veterinary Diagnostic Investigation. 32(2):301-311. https://doi.org/10.1177/1040638720907918.
DOI: https://doi.org/10.1177/1040638720907918

Interpretive Summary: Influenza A virus (IAV) is an important respiratory disease of swine that can cause significant economic losses for producers. The genome of IAV contains 8 gene segments that can be mixed or “reassorted” when an individual is infected with more than one strain of IAV. This process, called reassortment, results in new gene combinations in progeny viruses that may escape protection from prior vaccination, especially with inactivated vaccines. Inactivated and live attenuated influenza virus vaccines (LAIV) are available in the U.S. for use in swine. In this study, we examined the genetic makeup of IAV that were detected in porcine diagnostic submissions in the U.S. during 2018. These data identified gene combinations in viruses that were generated by reassortment events between circulating swine IAV and the strains included in the LAIV. The LAIV includes gene segments that were first characterized and isolated in U.S. swine in the late 1990s, but genetically similar viruses have not been detected in more than 10 years. These reassorted genotypes represent unique viruses compared to other recently circulating IAV, and may not be recognized by immunity against contemporary circulating strains. The reassortment between the LAIV strains and contemporary IAV has increased the genetic diversity among swine IAV, with potential impact to the swine industry if these novel strains spread to non-LAIV vaccinated herds.

Technical Abstract: Influenza vaccines historically have been multivalent, whole virus inactivated products. Recently, the first bivalent, intranasal, live attenuated influenza virus vaccine designated Ingelvac Provenza™ (LAIV) with H1N1 and H3N2 subtypes, was approved for use in swine. The Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) sequences over 1,500 H1 and H3 hemagglutinin (HA) genes from IAV each year from porcine respiratory diagnostic cases. From January 8 to October 11 2018, IAV HA sequences demonstrating 99.5-99.9% nucleotide homology to the H1 HA or 99.4-100% nucleotide homology to the H3 HA parental strains in the LAIV were detected in 5.2% (58/1116) of porcine respiratory cases (H1 HA A/swine/Minnesota/37866/1999(H1N1) (MN99); and H3 HA A/swine/Texas/4199-2/1998(H3N2) (TX98)). Thirty-five cases had associated epidemiological information that indicated they were submitted from 11 states representing 31 individual sites and 17 production systems in the United States (US). There were 6 cases from 3 production systems that reported no use of LAIV. Seven cases had evidence of LAIV co-detection with wild-type IAV. Whole genome sequences (WGS) from 11 cases and another subset of 2 plaque-purified IAV were included in the study. Ten WGS, including one plaque-purified IAV, contained at least 4 or more internal genes from endemic IAV detected within the past 3 years. Phylogenetic analysis of WGS indicated reassortment occurred between vaccine virus and endemic field strains circulating in US swine. These data highlight the need and importance of continued IAV surveillance to detect emerging IAV with LAIV genes in the swine population.