A previously unknown mechanism in viral pathogenesis leading to effective new vaccines and post-exposure immune treatments of viral infections.

Investigations with the rabies virus identified a previously unknown mechanism of viral pathogenesis. After ultracentrifugation of a suspension of rabid dog brain and rabies vaccine strains, the supernatant was found to contain active components, as evaluated in an in vitro plaque test. The unexpected detection of active components in non-sedimented material prompted further research and the finding that these components, and not the complete virus, were responsible for paralysis and death. Vaccination of cattle with existing rabies vaccines showed that even low titres of antibodies against these components provided protection after challenge. In a control group of non-vaccinated cows, cows that had low titres of these antibodies survived rabies challenge. These low titres could not be detected with the usual serum neutralization test in mice but only with a plaque reduction test, which is more sensitive. A hyperimmune serum raised in rabbits against active components isolated from the brain of a rabid dog was injected intracerebrally into mice that had been previously injected intramuscularly with a rabies virus. This delayed post-exposure treatment was still effective against advanced rabies (virus already in the brain, but not yet paralytic symptoms). This promising finding makes the development of a new inactivated rabies vaccine possible and opens the way for post-exposure treatment for humans, particularly in developing countries where rabies is still a major problem. The role of these active components in other viral diseases, such as human immunodeficiency virus, should be investigated.