Immunization with influenza A NP-expressing vaccinia virus recombinant protects mice against experimental infection with human and avian influenza viruses

• Published in: Archives of virology 2006-05, Vol.151 (5), p.921-931
• Main Authors: ALTSTEIN, A. D, GITELMAN, A. K, SHNEIDER, A. M, SMIRNOV, Y. A, PISKAREVA, L. M, ZAKHAROVA, L. G, PASHVYKINA, G. V, SHMAROV, M. M, ZHIRNOV, O. P, VARICH, N. P, ILYINSKII, P. O
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Viral - blood; Birds; Chick Embryo; Disease Models, Animal; Female; Humans; Infections; Influenza; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - growth & development; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H5N2 Subtype - growth & development; Influenza A Virus, H5N2 Subtype - immunology; Influenza in Birds - prevention & control; Influenza Vaccines - administration & dosage; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Influenza virus; Influenza, Human - prevention & control; Lung - virology; Lungs; Mice; Mice, Inbred BALB C; Nucleoproteins - genetics; Nucleoproteins - immunology; Ornithine Carbamoyltransferase - genetics; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Peptides; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - immunology; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - immunology; Viral Core Proteins - genetics; Viral Core Proteins - immunology; Virology; Viruses
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-005-0676-9

Two-fold immunization of Balb/c mice with a vaccinia virus recombinant expressing the NP protein of influenza A/PR8/34 (H1N1) virus under the control of a strong synthetic promoter induced specific antibodies and protected animals against low-dose challenge by mouse-adapted heterosubtypic variants of human A/Aichi2/68 (H3N2) and avian A/Mallard/Pennsylvania/10218/84 (H5N2) influenza virus strains. The surviving immunized animals had lower anti-hemagglutinin antibody titers compared to non-immunized mice. There was no difference in viral titers in lungs of immunized and non-immunized animals that succumbed to the infection. In order to try to increase immune system presentation of NP-protein-derived peptides, and thereby increase their immunogenicity, we constructed another vaccinia-based NP-expressing recombinant containing a rapid proteolysis signal covalently bound to the NP protein. This sequence, derived from the mouse ornithine decarboxylase gene has been shown to increase degradation of various proteins. However, we found that when used as part of a recombinant NP, this signal neither increased its proteolytic degradation, nor was it more efficient in the induction of a protective response against influenza infection.