Prospects of using conservative linear B-cell epitopes of influenza virus A neuraminidase for induction of cross-protective immune response

Abstract

BACKGROUND: Influenza is a dangerous, widespread infectious disease that takes thousands of lives during annual epidemics, and also causes significant damage to the country’s economy. The most effective means of fighting the influenza virus is vaccination of the population. Due to the variability of influenza viruses, the strain composition of influenza vaccines must be updated annually. In this regard, an urgent task is to improve the existing influenza vaccines in order to expand their spectrum of action. One of the promising approaches is the targeted induction of the humoral immune response to the conservative linear epitopes of influenza A virus neuraminidase.

AIM: This project is aimed at assessing the immunogenicity and cross-protective activity of conserved neuraminidase epitopes in order to select promising targets for the targeted design of broad-spectrum influenza vaccines.

MATERIALS AND METHODS: Peptides corresponding to linear B-cell epitopes of neuraminidase were chemically synthesized de novo. The peptides were conjugated with keyhole limpet hemocyanin. CBA mice were immunized and challenged with A/PR/8/34 (H1N1) and A/Philippines/2/1982 (H3N2) viruses at a dose of 3 LD₅₀. The survival rate of the animals was assessed within 14 days after infection. The immunogenicity of the peptides was assessed in a standard enzyme-linked immunosorbent assay using the recombinant neuraminidase proteins of the viruses A/California/07/2009 (H1N1) and A/Hong Kong/4801/2014 (H3N2) as antigen.

RESULTS: Immunization of neuraminidase with peptides MNPNQKIITIGS and ILRTQESEC, but not DNWKGSNRP, protected mice from lethality caused by the H1N1 and/or H3N2 virus. The protective potential of the peptides correlated with the levels of antineuraminidase antibodies after immunization.

CONCLUSIONS: The presence of a cross-protective potential in two conserved linear B-cell epitopes of influenza A neuraminidase (MNPNQKIITIGS and ILRTQESEC) allows them to be recommended as a target for the development of a broad-spectrum influenza vaccine.

Keywords

influenza A virus / immune response / universal influenza vaccine / heterosubtypic immune response / antineuraminidase antibodies / linear B-cell epitopes

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RIGHTS & PERMISSIONS

Sychev I.А., Kopeikin P.M., Tsvetkova E.V., Shamova O.V., Desheva Y.A., Isakova-Sivak I.N.