Protection elicited by a replication-defective adenovirus vector expressing the tick-borne encephalitis virus non-structural glycoprotein NS1.
Tick-borne encephalitis virus (TBEV) encodes a conserved, immunogenic, non-structural protein NS1 that is glycosylated and secreted from infected cells in an oligomeric form. An adenovirus recombinant, RAd51, expressing high levels of TBEV NS1 has previously been demonstrated to protect mice against a lethal challenge with TBEV. We show here that BALB/c mice infected with TBEV experienced a transient viraemia between days 3 to 5 post-inoculation that was detectable prior to the encephalitic phase of infection. Mice vaccinated with RAd51 were protected against both the viraemic and encephalitic infections associated with the TBEV challenge. Protection was demonstrated to be due to NS1 synthesized de novo from RAd51 in the vaccinated mice. Since TBEV NS1 is expressed on the cell surface, antibody-dependent complement-mediated cytolysis (CMC) of infected cells was considered as a possible mechanism of protection. Vaccination with the recombinant adenovirus proved to be effective in a mouse strain carrying a genetic deletion in the complement receptor C5. CMC is therefore not an essential component of the observed protective immune response.
Jacobs
S C
SC
Molecular Virology Group, PHLS Centre for Applied Microbiology and Research, Salisbury, Wiltshire, U.K.
Stephenson
J R
JR
Wilkinson
G W
GW
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology*; D004669:Encephalitis Viruses, Tick-Borne / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D004675:Encephalitis, Tick-Borne / Q000276:immunology / Q000503:physiopathology; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis* / Q000276:immunology; D014765:Viral Vaccines; D014766:Viremia / Q000276:immunology / Q000503:physiopathology; D014779:Virus Replication / Q000235:genetics*
D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines