Modulation of experimental autoimmunity: treatment of adjuvant arthritis by immunization with a recombinant vaccinia virus.
Live recombinant vaccinia viruses, expressing antigens from pathogenic microorganisms, are studied for their use as vaccines designed for the protection against infectious diseases. Infections with these vaccinia virus recombinants, expressing proteins or epitopes from viruses, parasites, or bacteria, have resulted in the development of specific neutralizing antibodies or cytotoxic T lymphocytes. Here, we describe the generation of a recombinant vaccinia virus expressing the mycobacterial 65-kDa heat shock protein (HSP65). A vaccinia recombinant virus was constructed by placing the gene for the Mycobacterium bovis BCG HSP65 under control of a vaccinia virus promoter and inserting this mycobacterial gene in the thymidine kinase locus of the vaccinia virus genome. Mycobacterial HSP65 is a critical antigen in the autoimmune model of adjuvant arthritis induced in Lewis rats by the immunization with Mycobacterium tuberculosis. We report the induction of immunity directed to this mycobacterial HSP65 by testing for the presence of specific antibodies and T-cell proliferation. Furthermore, induction of such immunity resulted in a reduction of arthritis severity when given to rats before or, even more interestingly, during development of arthritis. Disease reduction was not found after administration of HSP65 in the absence of vaccinia virus as a vector when given during arthritis development. Therefore, recombinant vaccinia virus may offer new prospectives for specific intervention in autoimmunity.
Hogervorst
E J
EJ
Department of Immunology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
Schouls
L
L
Wagenaar
J P
JP
Boog
C J
CJ
Spaan
W J
WJ
van Embden
J D
JD
van Eden
W
W
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D015551:Autoimmunity / Q000276:immunology*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013937:Thymidine Kinase / Q000235:genetics; D014614:Vaccines, Synthetic / Q000235:genetics*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D004269:DNA, Bacterial; D006360:Heat-Shock Proteins; D014614:Vaccines, Synthetic; D013937:Thymidine Kinase