Location: Virus and Prion Research
Project Number: 5030-32000-120-20-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jun 2, 2018
End Date: Aug 30, 2020
1. Characterize the antigenic impact of genetic changes in the hemagglutinin protein of influenza A viruses in swine and assessing individual and population immunity to current antigenic variants. 2. Utilize hemagglutination inhibition assays with the NADC reference serum panel, antigenic cartography, and sequence analysis tools to quantify swine influenza A virus evolution in Brazil.
Objective 1. This project expands our previous work to antigenically characterize circulating influenza A viruses (IAV) in swine, with the goal of the new project to evaluate individual and population immunity to the circulating antigenic variants. The previous results established a baseline from which to measure ongoing antigenic evolution of contemporary swine isolates and quantify the distance from current human seasonal or swine vaccine strains. Antigenic cartography is a computational and mathematical tool developed at the Cooperator, providing a quantification and visualization of antigenic data generated by hemagglutination inhibition (HI) assays. Monovalent reference swine anti-sera generated at the ARS against representative viruses selected based on phylogenetic analyses of hemagglutinin (HA) genes and relative frequency of detection in the USDA IAV swine surveillance system will be used in HI assays. A limited number of amino acid changes have been demonstrated to be highly influential in the antigenic distances between viruses. The Cooperator will use automated sequence analysis to identify the antigenic motifs at these sites to more rapidly identify field viruses with a higher priority for testing using antigenic cartography. Longitudinal analysis of antigenic distances and amino acid sequence data will identify other additional amino acid positions that might be important to swine host and virus interactions. Such integrated analyses will be routinely applied to sequence data available in public databases. Antigenic cartography methods also have been extended to incorporate changes in immune profiles over time in individuals and populations. Here we aim to generate representative immunologic profiles individual pigs over time or of swine populations to determine the homologous and heterologous responses against the predominant antigenic groups of IAV in swine. Objective 2. The goal of this research is to use advanced phylogenetic analyses, protein modeling, and antigenic cartography resources to further characterize IAV from swine in Brazil. An additional 78 isolates were collected from pigs in Brazil during 2010-2014 that have not yet been sequenced and none of the isolates have been antigenically characterized by the ARS reference panel and antigenic cartography. Brazil collaborator will perform whole genome sequencing on representatives of the 78 new isolates. USDA and Cooperator will assist with sequence analysis and provide well-defined reference sequences for phylogenetic characterization. USDA will provide the NADC H1 and H3 antisera panels and reference viruses for HI assays for the antigenic characterization to be performed at Cooperator facility. The use of a common set of sera that includes current human seasonal viruses will allow incorporation of the Brazilian swine viruses into what is known for the United States and other reporting countries to gain a global understanding of the antigenic diversity of swine IAV.