Immunological basis for protection in a murine model of tick-borne encephalitis by a recombinant adenovirus carrying the gene encoding the NS1 non-structural protein.
The humoral immune response to flaviviruses is mainly directed to the major envelope protein, E, and a glycosylated non-structural protein, NS1. Cell-mediated immune responses, however, appear to be directed mainly against non-structural proteins. Experiments described here show that a defective recombinant adenovirus (Rad51) containing the gene encoding the NS1 protein of tick-borne encephalitis virus can induce a strong protective immune response against several pathogenic tick-borne flaviviruses in an experimental animal model, and can enhance the efficacy of conventional vaccine preparations. A protective immune response against a lethal virus challenge can also be induced by the passive transfer of antibodies, B cells or T cells from animals vaccinated with Rad51. Raised levels of non-neutralizing antibodies and cytokines associated with a T helper cell-type 1 immune response are also observed. These data demonstrate the importance of non-structural viral proteins in the protective immune response against flaviviruses and support the use of non-structural viral proteins as vaccine components.
Timofeev
A V
AV
Chumakov Institute of Poliomyelitis and Viral Encephalitides RAMS, Moscow Region, Russia.
Ozherelkov
S V
SV
Pronin
A V
AV
Deeva
A V
AV
Karganova
G G
GG
Elbert
L B
LB
Stephenson
J R
JR
D000256:Adenoviridae / Q000235:genetics; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D003673:Defective Viruses / Q000235:genetics; D004195:Disease Models, Animal; D004669:Encephalitis Viruses, Tick-Borne / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D004675:Encephalitis, Tick-Borne / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D005814:Genes, Viral; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000276:immunology*; D014765:Viral Vaccines / Q000494:pharmacology
D000914:Antibodies, Viral; D016207:Cytokines; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines