The mechanism of active cerebral immunity to equine encephalomyelitis virus; the local antigenic booster effect of the challenge inoculum.

The fate of W.E.E. virus has been followed in the brains of mice vaccinated to such an extent that they failed to resist a large intracerebral challenge dose of a viral variant with a rapid rate of multiplication but were fully protected against a similar amount of a "slow" strain. The growth rate of the "fast" variant in vaccinated animals paralleled that in non-vaccinated ones at a slightly lower level. The "slow" strain also multiplied, but its rate of growth was depressed. Nevertheless, it persisted for 4 days at a level 100-fold higher than its initial titer. After the 4th day the virus was no longer demonstrable and was replaced by neutralizing antibody which rose so high that the serum antibody/brain antibody ratio was reduced from a "physiological" value of about 200/1 to less than 10/1. Antibody persisted in brain tissue in high titer until at least 127 days after challenge inoculation. The shift in the serum/brain ratio of neutralizing antibody was paralleled by a similar shift in the ratio of complement-fixing antibody. The neutralizing antibody in brain tissue, like that in serum, followed the "percentage law" on dilution of underneutralized mixtures. In mice immunized with small doses of vaccine, the intracerebral challenge inoculum induced a significantly greater local immune response than in those immunized to a higher degree. Mice with very low grade immunity were found more resistant to large amounts of virus than to small amounts. This "paradoxical" response to challenge was explained as due to the antigenic booster effect exerted by amounts of virus in excess of that utilized to initiate infection which were present in large inocula but absent in small doses. The broader relation of these findings to the problem of antiviral immunity has been discussed.