Pathogenicity and immunogenicity for mice of temperature-sensitive mutants of vesicular stomatitis virus

Temperature-sensitive (ts) mutants of vesicular stomatitis (VS) virus were tested for their pathogenicity and immunogenicity in weanling mice. Compared with the wild-type virus (ts(+)), ts mutants representing genetic complementation groups I, II, and IV were considerably less pathogenic for mice infected by the intracerebral route and caused few deaths after intranasal inoculation. Mice were completely resistant to ts(+) and ts mutants by the intraperitoneal route. Resistance to intracerebral challenge with ts(+) VS virus was only minimal in mice vaccinated intraperitoneally with ts(+) or ts mutants and only moderate in mice vaccinated intranasally with three ts mutants. Intranasal vaccination, particularly with group IV mutants, resulted in solid immunity within 3 days to intranasal challenge with ts(+) virus. VS viral neutralizing antibody was present in the bronchial secretions of mice by 12 h after intranasal inoculation of mutant ts IV44; the bronchial antibody titers declined to undetectable levels between 3 and 7 days after vaccination. Neutralizing antibody was detected in the serum of mice by the third day after intranasal vaccination with ts IV44 and persisted at high level for at least 11 days. Certain classes of ts mutants would appear to be promising candidates for use as attenuated, live virus vaccines.