Detection of live attenuated influenza vaccine virus and evidence of reassortment in the U.S. swine population

Abstract

Influenza vaccines historically have been multivalent, whole virus inactivated products. The first bivalent, intranasal, live attenuated influenza vaccine (LAIV; Ingelvac Provenza), with H1N1 and H3N2 subtypes, has been approved for use in swine. We investigated the LAIV hemagglutinin ( HA) sequences in diagnostic cases submitted to the Iowa State University Veterinary Diagnostic Laboratory and potential vaccine virus reassortment with endemic influenza A virus (IAV) in swine. From January 3 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 58 of 1,116 (5.2%) porcine respiratory cases (H1 HA A/swine/Minnesota/37866/1999[H1N1; MN99]; H3 HA A/swine/Texas/4199-2/1998[H3N2; TX98]). Nine cases had co-detection of HA genes from LAIV and wild-type IAV in the same specimen. Thirty-five cases had associated epidemiologic information that indicated they were submitted from 11 states representing 31 individual sites and 17 production systems in the United States. Whole genome sequences from 11 cases and another subset of 2 plaque-purified IAV were included in our study. Ten whole genome sequences, including 1 plaque-purified IAV, contained at least one internal gene from endemic IAV detected within the past 3 y. Phylogenetic analysis of whole genome sequences indicated that reassortment occurred between vaccine virus and endemic field strains circulating in U.S. swine. Our data highlight the need and importance of continued IAV surveillance to detect emerging IAV with LAIV genes in the swine population.

Influenza A Virus in Swine: Epidemiology, Challenges and Vaccination Strategies

“…LAIVs are the only vaccines that generate mucosal immunity and are a promising tool in the prevention of IAV-S, but they can replicate in the host and reassortment with field strains cannot be ignored. In fact, reassortment capabilities of LAIVs were demonstrated in experimental conditions and in the field (115,130). Although this reassortment did not result in increased virulence, further research will be needed to evaluate the impact of this process on influenza A virus's epidemiology.…”

“…This vaccine was efficacious in reducing virus nasal shedding after challenge with heterologous strains, either H1N1 or H3N2, with and without presence of MDAs (113,114). However, a recent phylogenetic study done in the US with samples collected in 2018 found reassortant strains containing LAIV vaccine strain genes in combination with US endemic field strain genes (115). These data indicate that viral reassortment is possible with LAIV vaccines.…”

Future perspectives on swine viral vaccines: where are we headed?

“…In experimental trials this vaccine showed significant reduction of nasal IAV shedding when pigs were challenged 12 weeks after vaccination [ 26 ]. Recently, evidence of re-assortment of the live attenuated IAV vaccine virus with endemic field strains circulating in the US was detected [ 27 ]. The report raises concerns over the safety of this particular vaccine.…”

“…A pig virus that is commonly controlled by use of inactivated vaccines is IAV [ 31 ]. This may be in part due to the perceived risk of live vaccines giving way to reassortant viruses or reversion to virulence [ 27 ]. Any new IAV variant (recombination, re-assortment) could be detrimental to pigs but also other species including humans due to its cross-species tropism.…”

Shedding and transmission of a live attenuated influenza A virus vaccine in pre-weaned pigs under field conditions

“…Despite our findings of limited shedding from vaccinated pigs to non-vaccinated pigs with direct contact and sentinels with indirect contact, it is important to emphasize the need to use LAIV when there are no endemic swine IAV viruses circulating in the population. Reassortment between endemic swine IAV and LAIV has been documented [33] and it is possible that reassortment could still take place in situations of limited LAIV shedding. Nevertheless, efforts need to be made to minimize presence of endemic IAV viruses at time of vaccination with LAIV.…”