The relationship between immunity and the pathology of the CNS of mice infected with the CVS strain of rabies.

The CVS strain of rabies was used both for the production of immunity and as a challenge virus. The immunity induced in mice irrespective of the route of inoculation, whether i.p. or i.c., proved to be dose dependent and disappeared after a period of time. Immunization by the i.c. route had a longer lasting effect than by the i.p. route. Animals surviving immunization and challenge had, in addition to neutralizing antibodies in the serum, also high levels of antibodies in the brain. After challenge, depending on the dose and the time interval between immunization and challenge, a proportion of mice developed signs of disease, from which the majority died, but some survived in a crippled state. The CVS strain of rabies inoculated into susceptible mice gave rise to acute signs of disease and mortality. The lesions in the brain of such mice consisted of both inflammatory and degenerative changes and included marked microglial proliferation and above all a constant severe astrogliosis. In immunized mice the relationship between immunity and the pathological changes was clearly marked. Susceptible mice had inflammatory lesions in the form of a scanty meningeal exudate and perivascular cuffings composed of 1-2 layers whereas the degenerative lesions were confined only to a proportion of pyramidal cells of the hippocampus. Mice immunized with an inactivated vaccine, or challenged a very long time after immunization, had very scanty inflammatory changes and very severe necrosis of parts of the brain including the hippocampus. On the other hand, mice that received multiple immunizing doses of live virus had very limited degenerative changes in the brain, but showed marked inflammation with copious meningeal and chorioid plexus infiltrations and perivascular cuffings, consisting of a large number of layers of infiltrating cells. A considerable proportion of non-clinical survivors and all mice that survived the clinical disease had lesions in the brain that had a tendency after a lapse of time to become subacute, leading to focal partial or complete sclerosis, mainly of the hippocampus. The astrocytic reaction appeared to play a major role in the formation of the subacute lesions in the brain. All the mice that developed brain lesions were considered to have survived an active rabies brain infection. This was confirmed by the isolation of virus from brains of mice during the first week after challenge.