Influenza A Virus Field Surveillance at a Swine-Human Interface

Abstract

While working overnight at a swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, Nanopore sequenced 13 IAV genomes from samples we collected, and predicted in real time that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current prepandemic candidate vaccine viruses (CVVs). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 h after unpacking the mobile lab. Exhibition swine are a known source for zoonotic transmission of IAV to humans and pose a potential pandemic risk. Genomic analyses of IAV in swine are critical to understanding this risk, the types of viruses circulating in swine, and whether current vaccines developed for use in humans would be predicted to provide immune protection. Nanopore sequencing technology has enabled genome sequencing in the field at the source of viral outbreaks or at the bedside or pen-side of infected humans and animals. The acquired data, however, have not yet demonstrated real-time, actionable public health responses. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes, A(H1N1), A(H3N2), and A(H1N2). Analysis of the hemagglutinin (HA) sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 of these viruses and the most closely related CVV. As an exercise in pandemic preparedness, all sequences were emailed to CDC collaborators who initiated the development of a synthetically derived CVV. IMPORTANCE Swine are influenza virus reservoirs that have caused outbreaks and pandemics. Genomic characterization of these viruses enables pandemic risk assessment and vaccine comparisons, though this typically occurs after a novel swine virus jumps into humans. The greatest risk occurs where large groups of swine and humans comingle. At a large swine exhibition, we used Nanopore sequencing and on-site analytics to interpret 13 swine influenza virus genomes and identified an influenza virus cluster that was genetically highly varied to currently available vaccines. As part of the National Strategy for Pandemic Preparedness exercises, the sequences were emailed to colleagues at the CDC who initiated the development of a synthetically derived vaccine designed to match the viruses at the exhibition. Subsequently, this virus caused 14 infections in humans and was the dominant U.S. variant virus in 2018.

Improvements to the ARTIC multiplex PCR method for SARS-CoV-2 genome sequencing using nanopore

“…Real-time, genomic surveillance has become a central component in the management of outbreaks of emerging infectious diseases and has been successfully deployed to understand the transmission patterns of Ebola virus [ 1 , 2 ], Lassa virus [ 3 ], Yellow fever virus [ 4 , 5 ] and Influenza [ 6 ]. Viral genomes can be used to estimate the rate of viral evolution, monitor circulating lineages as well as identifying any signs of adaptation to hosts, treatments or vaccines.…”

Characterization of Swine Influenza A(H1N2) Variant, Alberta, Canada, 2020

“…A zoonotic H1α-3 H1N2v virus strain (A/Ohio/24/2017/H1N2) was isolated from a human in the United States in 2017 ( 32 ). The A/Ohio/24/2017/H1N2 and A/Alberta/01/2020 strains share high nucleotide identity (91.3%–96.6%) within 8 major genes; however, this proportion is lower than that of other H1N2 strains ( Table ).…”

Rapid multiplex MinION nanopore sequencing workflow for Influenza A viruses

“…The suitability of sequencing approaches for field surveillance was demonstrated with swine influenza viruses and the comparison to Illumina sequencing library strategies show comparable results with longer total analysis time and specific hands-on-time, respectively [16]. The use of multiplexing strategies is preferable due to the advantages of barcoding in higher throughput, better cost efficiency and decreased sequencing run time.…”