Matrix Protein Gene Variants of Two Distinct Serotypes of rVSV Make Effective Viral Vectors for Prime-Boost Vaccination

Abstract

Recently, we developed attenuated VSV vectors by introducing temperature sensitive (ts) mutations in the M gene in both VSV Indiana and New Jersey serotypes. The newly generated M gene mutants of rVSV vectors are rVSVInd(GML) with mutations of 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 purpose was to examine the immunogenicity of the new ts M gene mutant of rVSVInd and attenuated M gene mutants ofrVSVNJas vaccine vectors against HIV-1 proteins. We generated attenuated rVSVs carrying HIV-1 gag, pol, and env genes. We immunized mice with various prime-boost vaccination regimens. CD8+ T cell responses and humoral immune responses in the vaccinated mice were examined. Priming with rVSVInd(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 same vaccination regimen also induced strong humoral immune responses against the HIV-1 Gag and Env proteins. We conclude that rVSVInd(GML) priming followed by rVSVNJ(GMM) boosting is the best vaccination regimen for optimum B cell and T cell adaptive immune responses against inserted foreign gene products when the newly attenuated rVSVInd and rVSVNJ are used.