C. Yong Kang
Western University,Canada
Title: Engineering of Highly Efficient Recombinant Viral Vectors for Development of Prime-Boost Vaccines Against Viral Diseases
Biography
Biography: C. Yong Kang
Abstract
In order to induce the maximum immune responses, the priming recombinant viral vector should be antigenically distinct from the boost vaccine vector. We have engineered safer and highly efficient recombinant vesicular stomatitis virus (VSV) vaccine vectors using two antigenically distinct Indiana serotype (VSVInd) and New Jersey serotype (VSVNJ). The M51R mutation in the M gene of VSVInd was combined with a temperature sensitive mutation of the VSVInd Orsay tsO23 for priming vaccine vector [rVSVInd(GML)]. In addition, we have engineered VSVNJ vaccine vector by combining M48R+M51R mutation with G22E and L110F mutations in the M gene of VSVNJ [VSVNJ(GMML)] for boosting vaccine vector. The combined mutations of G21E/M51R/L111A in the M protein of VSVInd [rVSVInd(GML)] significantly reduced the burst size of the virus by up to 10,000 fold at a semi-permissive temperature of 37°C without affecting the level of protein expression. Mice injected with one million infectious particles of rVSVInd(GML) into the brain showed no neurological dysfunctions or any other adverse effects. In contrast, only one thousand wild-type VSVInd killed mice within four days. To examine the CD8+ T cell and B cell responses against the proteins of interest expressed from the rVSV vectors, we generated rVSVs with HIV-1gag, pol and/or env genes. From the various vaccination regimens tested in mice, priming with rVSVInd(GML)-HIV-1gag, pol, and/or env and boosting with rVSVNJ(GMML)-HIV-1gag, pol, and/or env induced the strongest CD8+ T cell immune responses against HIV-1 Gag, Pol, and Env proteins. The same vaccination regimen also induced strong humoral immune responses against HIV-1 Gag and Env proteins in mice. This is our unique platform technology and is useful for development of vaccines against many other viral diseases.
