Inhibition of allergic encephalomyelitis in marmosets by vaccination with recombinant vaccinia virus encoding for myelin basic protein.
A primary demyelinating form of experimental allergic encephalomyelitis (EAE) resembling human multiple sclerosis (MS) occurs in Callithrix jacchus marmosets following immunization with human white matter. Participation of a T-cell immune response against myelin basic protein (MBP) in this disease model is supported by observations of increased reactivity against MBP in PBMC and of adoptive transfer of an inflammatory form of EAE by MBP-reactive T-cells. To evaluate the effects of ectopic presentation of MBP on marmoset EAE, animals were vaccinated prior to induction of EAE by subcutaneous injection of attenuated strains of vaccinia virus genetically engineered to contain either the entire coding sequence for human MBP (vT15) or the equine herpes virus glycoprotein gH gene (vAbT249). Vaccination with vT15 was followed by transient cytoplasmic and surface membrane expression of MBP in circulating PBMC (15-45 days). The onset of clinical EAE after immunization (pi) was markedly delayed in vT15-vaccinated animals (37-97 days pi, n = 4) compared to vAbT249-vaccinated controls (14-18 days pi, n = 3). Proliferative responses against MBP but not against vaccinia antigens or phytohemagglutinin were suppressed in protected animals. Thus, development of attenuated live viruses carrying genes for myelin antigens could be useful for induction of immunologic tolerance and for modulation of autoimmune demyelination.
Genain
C P
CP
Department of Neurology, University of California, San Francisco 94143-0435, USA. claudeg@itsa.ucsf.edu
Gritz
L
L
Joshi
N
N
Panicali
D
D
Davis
R L
RL
Whitaker
J N
JN
Letvin
N L
NL
Hauser
S L
SL
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002144:Callithrix; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000517:prevention & control*; D004676:Myelin Basic Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000627:therapeutic use*; D014615:Vaccinia / Q000378:metabolism / Q000473:pathology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000627:therapeutic use*
D000906:Antibodies; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004676:Myelin Basic Protein; D014614:Vaccines, Synthetic; D014765:Viral Vaccines