Novel Vaccine for Respiratory Syncytial Virus
T2017-299 Recombinant vesicular stomatitis virus (rVSV) vaccines to fight against respiratory syncytial virus (RSV) infections.
Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract illness (ALRI) in infants, children, and the elderly, and often leads to fatal bronchiolitis and pneumonia. About 3.4 million children under the age of five are hospitalized each year due to an acute RSV infection. About 200,000 deaths occur annually worldwide, with most deaths occurring in children under one year of age. Currently, there is no licensed vaccine for RSV.
OSU and Nationwide Children’s Hospital inventors led by Dr. Stefan Niewiesk have developed a novel rVSV-based codon-optimized viral antigen vaccine candidates with single or multiple RSV antigens for prevention of RSV infection. The antigens of choice include all four major RSV structural proteins (glycoprotein [G], fusion protein [F], Nucleoprotein [N] and M2-1) which are responsible for induction of immune responses in an RSV infected individual. Dr. Niewiesk's team has developed four types of recombinant VSVs individually expressing one of the four above mentioned antigenic structural proteins. For expression of G protein, instead of cloning wildtype G protein gene in the rVSV, we have cloned a codon optimized version of the gene. Codon optimization of a gene enables higher expression of the vaccine antigen (G protein, in this case). Therefore, from the same dose of the vaccine, a codon optimized gene expressing VSV produces significantly higher levels of the antigen protein resulting in dose amplification, so that the required dose of the rVSV can be significantly reduced. Further, in the context of RSV infection, G protein is produced in two forms (membrane bound [mG] and secretory [sG] forms). rVSVs expressing both forms have been produced and pre-clinical in vivo efficacy studies in a cotton rat animal model has been conducted. The results indicated that mG induced protective immunity but not the sG. F protein is involved in the fusion of the virus to the cell membrane and has a higher number of neutralizing epitopes, antigenic sites and T-cell epitopes than G protein, thus, making it as the most attractive vaccine candidate. N and M2-1 proteins have been shown to contain several putative sites of T-cell epitopes inducing cell mediated immunity, which is responsible for clearance of the virus from the body.
- Vaccine for RSV
- Recombinant vaccine to treat RSV
- Positive immunity to RSV in animal models