Pathogenicity and Immunogenicity for Mice of Temperature-Sensitive Mutants of Vesicular Stomatitis Virus

Abstract

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.

In vivo biodistribution of a highly attenuated recombinant vesicular stomatitis virus expressing HIV-1 Gag following intramuscular, intranasal, or intravenous inoculation

“…While mice are not considered a natural host for VSV, they have been used as an animal model for studying VSV pathogenesis for over 70 years [38]. The exquisite sensitivity of mice to VSV infection has proven them as a valuable research tool for assessing virulence of wild type and attenuated strains of VSV [12][13][14][15][16][17][18][19][20]. While the neurovirulence associated with VSV infection in mice has been well studied, there has not been much advancement in the understanding of the biodistribution of VSV in mice since the pioneering work of Sabin and Olitsky in the 1930s [39][40][41][42][43].…”

“…VSV infection of humans is typically either asymptomatic or causes a mild influenza-like illness [6]. Among small mammals, mice are readily infected experimentally via a variety of inoculation routes and thus have served as a tractable model for immunogenicity, pathogenicity, neurotropism and neurovirulence studies [12][13][14][15][16][17][18][19][20].…”

Recombinant Isfahan Virus and Vesicular Stomatitis Virus Vaccine Vectors Provide Durable, Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge

“…However, the safety of rVSIV vectors initially was a concern because both VSIV and the New Jersey serotype of VSV (vesicular stomatitis New Jersey virus [VSNJV]) are known to have neurotropic properties in young mice and can cause neurological disease following intracranial (i.c.) inoculation of cows and horses (32)(33)(34)(35). A pilot NHP neurovirulence (NV) study indicated that a prototypic rVSIV vector was insufficiently attenuated for clinical evaluation (36)(37)(38).…”

Neurovirulence and Immunogenicity of Attenuated Recombinant Vesicular Stomatitis Viruses in Nonhuman Primates

“…Protective, SHIV-specific immune responses were increased when rVSIV and MVA vectors were administered in a heterologous prime-boost regimen (40). However, VSIV and the New Jersey (NJ) serotype of VSV are known to have neurotropic and neurovirulence (NV) properties in young mice (41)(42)(43)(44) and can be lethal following direct intracranial (i.c.) inoculation of livestock (45).…”