Immunization with influenza A NP-expressing vaccinia virus recombinant protects mice against experimental infection with human and avian influenza viruses.
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.
Altstein
A D
AD
Institute of Gene Biology RAS, Moscow, Russia. altstein.ad@relcom.ru
Gitelman
A K
AK
Smirnov
Y A
YA
Piskareva
L M
LM
Zakharova
L G
LG
Pashvykina
G V
GV
Shmarov
M M
MM
Zhirnov
O P
OP
Varich
N P
NP
Ilyinskii
P O
PO
Shneider
A M
AM
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001717:Birds; D002642:Chick Embryo; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000254:growth & development / Q000276:immunology*; D053125:Influenza A Virus, H5N2 Subtype / Q000254:growth & development / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000517:prevention & control; D007251:Influenza, Human / Q000517:prevention & control; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D009954:Ornithine Carbamoyltransferase