Journal of Vaccines & Vaccination

Creation of highly efficient recombinant viral vectors for development of prime-boost vaccines: Matrix protein gene variants of two antigenically distinct serotypes of vesicular stomatitis virus are ideal vaccine vectors

6^th Euro Global Summit and Expo on Vaccines & Vaccination

August 17-19, 2015 Birmingham, UK

Chil-Yong Kang

Keynote: J Vaccines Vaccin

Abstract:

In order to induce the maximum immune responses by vaccination, the priming recombinant viral vector should be antigenically
distinct from the boost vaccine vector. A priming vaccine vector will most likely induce neutralizing antibodies which will neutralize
the boosting vaccine vector if one uses the same vector for the prime-boost. One of the rhabdo viruses, the vesicular stomatitis virus
(VSV), offers the ideal system for prime-boost vaccine vectors. We have generated safer and more highly efficient recombinant 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
[designated as rVSVInd (GML)]. In addition, we have generated two new VSVNJ vaccine vectors by combining M48R+M51R mutation
with G22E and L110F mutations in the M gene of VSVNJ, [designated as rVSVNJ (GMM) and VSVNJ(GMML)] for boosting. 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. The BHK21 cells
and human neuroblastoma, SH-SY5Y cells infected with rVSVInd (GML), rVSVNJ(GMM) and rVSVNJ(GMML) showed significantly
reduced cytopathic effects in vitro at 37°C, and mice injected with one million infectious particles of the viruses 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 protein of interest expressed from the new 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(GMM)-HIV-1gag, pol, and/or env and 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. The best humoral immune
responses against HIV-1 Gag and Env proteins were induced when two serotypes of rVSV were alternated for prime and boost
vaccination. Increasing vaccination doses of rVSVInd (GML)-HIV-1 gag, pol, and/or env, rVSVNJ (GMM)-HIV-1gag, pol, and/or env
and rVSVNJ (GMML)-HIV-1gag, pol and/or env induced stronger immune responses against HIV-1 Gag, Pol and Env proteins in
mice. As a boost vaccine vector, rVSVNJ (GMM), it induced better cellular and humoral immune responses against HIV-1 Gag and
Env proteins compared to rVSVNJ (GMML) with the same vaccine dose. This is our unique platform technology and is useful for
development of not only viral diseases but also bacterial diseases and even parasitic diseases.

Biography :

C Yong Kang, PhD, DSc, FRSC, is a Molecular Virologist and Professor of Virology in the Department of Microbiology and Immunology, Schulich School of Medicine and
Dentistry at the University of Western Ontario in Canada (1992-Present). He carried out his Post-graduate studies at McMaster University where he received a PhD in
Virology and his Post-doctoral training, Nobel Laureate in Physiology and Medicine at the University of Wisconsin-Madison. He went on to serve as a Professor of Virology in
the Department of Microbiology at the University of Texas, Professor and Chairman of the Department of Microbiology and Immunology at the University of Ottawa, and Dean
of Science at the University of Western Ontario. His research in molecular virology includes the development of viral-specific antiviral therapeutic agents and efficacious
vaccines against various human viral diseases including AIDS, hepatitis and hemorrhagic fever with renal syndrome. He has published 135 peer reviewed research papers
and 149 scientific proceedings and abstracts in the fields of virology, Immunology, molecular biology, and medicine. He holds nine international biotechnology patents that
cover over 70 countries. He also serves as a reviewer for the Journal of Virology, Journal of Infectious Diseases, Virus Research, Virology, Journal of Biological Chemistry,
Journal of Human Virology and Retrovirology, and Canadian Medical Association Journal.