1. Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope.
- Author
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Kim KH, Jung YJ, Lee Y, Park BR, Oh J, Lee YN, Kim MC, Jeeva S, and Kang SM
- Subjects
- Animals, Antibodies, Viral biosynthesis, Cross Protection, Epitopes chemistry, Epitopes immunology, Female, Hemagglutinin Glycoproteins, Influenza Virus genetics, Humans, Immunity, Cellular drug effects, Immunity, Humoral drug effects, Influenza A Virus, H1N1 Subtype drug effects, Influenza A Virus, H1N1 Subtype genetics, Influenza A Virus, H3N2 Subtype drug effects, Influenza A Virus, H3N2 Subtype genetics, Influenza A Virus, H3N2 Subtype immunology, Influenza A Virus, H5N1 Subtype drug effects, Influenza A Virus, H5N1 Subtype genetics, Influenza A Virus, H5N1 Subtype immunology, Influenza A Virus, H9N2 Subtype drug effects, Influenza A Virus, H9N2 Subtype genetics, Influenza A Virus, H9N2 Subtype immunology, Influenza Vaccines administration & dosage, Influenza Vaccines genetics, Mice, Mice, Inbred BALB C, Neuraminidase genetics, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections virology, Reassortant Viruses drug effects, Reassortant Viruses genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Vaccination methods, Vaccines, Inactivated, Viral Matrix Proteins genetics, Hemagglutinin Glycoproteins, Influenza Virus immunology, Influenza A Virus, H1N1 Subtype immunology, Influenza Vaccines biosynthesis, Neuraminidase immunology, Orthomyxoviridae Infections prevention & control, Reassortant Viruses immunology, Viral Matrix Proteins immunology
- Abstract
Influenza virus neuraminidase (NA) contains a universally conserved epitope (NAe, NA
222-230 ). However, no studies have reported vaccines targeting this NA conserved epitope and inducing antibodies recognizing NAe. The extracellular domain of M2 (M2e) is considered as an attractive target for a universal influenza vaccine. We generated recombinant influenza H1N1 viruses expressing conserved epitopes in hemagglutinin (HA) molecules: NAe (NAe-HA) or M2e (M2e-HA) within the HA head domain. Inactivated recombinant NAe-HA and M2e-HA viruses were more effective in inducing IgG antibodies specific for an inserted conserved epitope than live recombinant virus. Recombinant inactivated M2e-HA virus vaccination induced cross protection against H3N2 virus with less weight loss compared to NAe-HA and was more effective in inducing humoral and cellular M2e immune responses. This study provides insight into developing recombinant influenza virus vaccines compatible with current platforms to induce antibody responses to conserved poorly immunogenic epitopes., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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