The mechanism of active cerebral immunity to equine encephalomyelitis virus; influence of the rate of viral multiplication.

Continued serial brain-to-brain passage of strains of W.E.E. virus in mice has yielded variants which kill mice with increased rapidity. Their rate of multiplication in the mouse brain has been found to be correspondingly increased. At 1 hour after intracerebral inoculation of various amounts of W.E.E. virus, only 3.5 to 10 per cent of the expected amount of virus was recovered from the infected brains. In infected mouse brains, the period of active viral multiplication was preceded by a latent phase which lasted a considerably shorter time in the case of a "fast" than in that of a "slow" variant. In brains inoculated with various amounts in excess of minimal lethal doses the rates of multiplication tended to converge with the result that the maximum titer was reached after about the same period of time. After inoculation of smaller amounts, the rates of viral multiplication tended to parallel each other. Vaccinated mice may be fully resistant to maximal intracerebral doses of a slowly multiplying strain while they are not at all or only partly protected against a rapidly multiplying one derived from it. This difference is demonstrable even though fast and slow variants are, as far as can be tested, serologically identical. The difference in response may be masked if animals are immunized with relatively large doses of vaccine. The bearing of these findings on certain practical problems has been pointed out.