PROTECTION OF SJL J MICE FROM DEMYELINATING DISEASE MEDIATED BY THEILERS MURINE ENCEPHALOMYELITIS VIRUS/

Intracerebral infection with the DA strain of Theiler's murine encepha lomyelitis virus induces a chronic demyelinating. disease in SJL/J mic e. Intraperitoneal inoculation with either the wild-type DA virus or a n attenuated variant virus of DA, H7A6-2, results in protection from d evelopment of chronic demyelinating disease. Protective anti-viral imm une responses result in reduced viral titers and decreased inflammatio n in the central nervous system within the first week following intrac erebral challenge with virus. Development of protective immunity requi res the presence of B cells and CD4(+) T cells but does not require CD 8+ T cells. High titers of serum anti-viral IgG and neutralizing antib odies are induced following the intraperitoneal inoculation with the D A virus or H7A6-2 virus prior to challenge. While protection could not be transferred with immune serum from DA virus-infected mice or neutr alizing monoclonal antibodies, protection was correlated with increase d numbers of DA virus-specific plasma cells in the central nervous sys tem within the first week following intracerebral challenge. Protected mice also had enhanced levels of anti-DA virus IgG and neutralizing a ntibodies in the cerebral spinal fluid by 1 week following intracerebr al challenge with DA virus. Thus, we conclude that vaccination with li ve virus results in protection from chronic demyelinating disease by i nducing immune responses which are manifested in the central nervous s ystem and rapidly clear infection after intracerebral challenge with D A virus.