Antigenic variation in rabies and rabies-related viruses: cross-protection independent of glycoprotein-mediated virus-neutralizing antibody

Immunization experiments with vaccines prepared from the PM and ERA strains of rabies virus demonstrated that in mice, only ERA vaccine primes for an anamnestic response to the rabies-related strain Duvenhage (DUV6); in rabbits, both ERA and PM vaccines induced immunologic memory to DUV6 virus. In mice, ERA vaccine, but not an equal concentration of PM vaccine, conferred protection against a lethal challenge infection with DUV6 virus. This result indicated that the protective activity correlated with the vaccine's ability to induce immunologic memory. A vaccine prepared from a sequentially selected neutralization-resistant, multiple-variant virus conferred protection against challenge with the parental strain, a result indicating that antigenic variation of the glycoprotein may not be the sole factor in determining the relative efficacy of rabies prophylaxis. We found no correlation between titers of neutralizing antibody and mortality rates in mice immunized with purified glycoprotein from these viruses.