Recently, we developed attenuated VSV vectors by introducing temperature sensitive(ts) mutations in the M gene in both VSV Indiana and New Jersey serotypes. Thenewly generated M gene mutants of rVSV vectors are rVSVInd(GML) with mutationsof G21E, M51R, and L111F, rVSVNJ(GMM) with mutations of G22E, M48R, and M51R,and rVSVNJ(GMML) with mutations of G22E, M48R, M51R, and L110F. Our purposewas to examine the immunogenicity of the new ts M gene mutant of rVSVInd andattenuated M gene mutants of rVSVNJ as vaccine vectors against HIV-1 proteins. Wegenerated attenuated rVSVs carrying HIV-1 gag, pol, and env genes. We immunizedmice with various prime-boost vaccination regimens. CD8+ T cell responses andhumoral immune re... More
Recently, we developed attenuated VSV vectors by introducing temperature sensitive(ts) mutations in the M gene in both VSV Indiana and New Jersey serotypes. Thenewly generated M gene mutants of rVSV vectors are rVSVInd(GML) with mutationsof G21E, M51R, and L111F, rVSVNJ(GMM) with mutations of G22E, M48R, and M51R,and rVSVNJ(GMML) with mutations of G22E, M48R, M51R, and L110F. Our purposewas to examine the immunogenicity of the new ts M gene mutant of rVSVInd andattenuated M gene mutants of rVSVNJ as vaccine vectors against HIV-1 proteins. Wegenerated attenuated rVSVs carrying HIV-1 gag, pol, and env genes. We immunizedmice with various prime-boost vaccination regimens. CD8+ T cell responses andhumoral immune responses in the vaccinated mice were examined. Priming withrVSVInd(GML)-gag, pol, or env gene of HIV-1 and boosting with rVSVNJ(GMM)-gag,pol, or env gene or rVSVNJ(GMML)-gag, pol, or env gene induced the strongest CD8+cytotoxic T cell responses against the HIV-1 Gag, RT, and Env proteins. The samevaccintion regimen also induced strong humoral immune responses against theHIV-1 Gag and Env proteins. We conclude that rVSVInd(GML) priming followed byrVSVNJ(GMM) boosting is the best vaccination regimen for optimum B cell and T celladaptive immune responses against inserted foreign gene products when the newlyattenuated rVSVInd and rVSVNJ are used.
