|SITARAS, IOANNIS - Orise Fellow|
|DE JONG, MART - Wageningen University|
|PARRIS, DARREN - Orise Fellow|
Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2020
Publication Date: 10/22/2020
Citation: Sitaras, I., Spackman, E., De Jong, M.C., Parris, D.J. 2020. Selection and antigenic characterization of immune-escape mutants of H7N2 low pathogenic avian influenza virus using homologous polyclonal sera. Virus Research. 290:e198188. https://doi.org/10.1016/j.virusres.2020.198188.
Interpretive Summary: Avian influenza virus can be controlled in chickens by vaccination. However, the virus can mutate to escape the immunity produced by vaccines over time. The time necessary for the virus to mutate and which parts of the protein that can changes are not well characterized. To better understand how antibody can cause non-virulent strains of avian influenza to mutate, virus was treated with antibody from chickens and was grown in vitro for 30 cycles. During the 30 cycles of selection five changes were observed in the virus. These changes occurred progressively and were shown to allow the virus to escape the antibody; each change increased the ability of the virus to evade immunity. The data from this can be utilized to design vaccination programs which will be more effective because they will minimize the ability of the virus to escape immunity and will optimize the "life-span" of vaccines.
Technical Abstract: Understanding the dynamics of the selection of influenza A immune escape variants by serum antibody is critical for designing effective vaccination programs for animals, especially poultry where large populations have a short generation time and may be vaccinated with high frequency. In this report, immune-escape mutants of Low Pathogenic Avian Influenza (LPAI) H7N2 A/turkey/New York/4450/1994 were selected by serially passaging the virus in the presence of continuously-increasing concentrations of homologous polyclonal sera. Amino acid mutations were identified by sequencing the hemagglutinin (HA) gene, and the antigenic distance of the mutants to the parent strain was determined. A total of 5 amino acid mutations were observed over the course of 30 passages and appeared to be related to increases in serum concentration. The selected mutants have continuously drifted from the parent strain and the antigenic distance between them and the parent strain increased as the number of amino acid mutations accumulated. This selection system demonstrates how H7 avian influenza viruses behave under selection with homologous sera, and provides a glimpse of their evolutionary dynamics, which can be applied to developing vaccination programs that maximize the effectiveness of a vaccine over time.