IND-enabling studies of an intranasal, single-replication M2SR influenza vaccine

ABSTRACT Influenza (flu) virus, an NIAID category C priority pathogen, causes a respiratory disease resulting in over 200,000 hospitalizations and ~ 36,000 deaths per year in the US, while global influenza pandemics have resulted in as many as 50-100 million deaths worldwide. To address this threat to public health, annual vaccination is recommended for all individuals aged over 6 months in the US. However, currently available vaccines are lacking in efficacy. CDC’s vaccine effectiveness (VE) estimates for the 2014-2015 influenza season was only 23%. The reduced protection was attributed to the fact that the circulating viruses had drifted from the H3N2 vaccine virus recommended for vaccine production. In fact overall VE from 2005-2016 ranges from 10% to 60% at best. Current influenza vaccines, live or inactivated, offer suboptimal protection when matched and do not provide protection when the vaccine is mismatched. FluGen has developed a novel M2-deficient influenza vaccine (M2SR) that provides effective heterosubtypic protection in animal models. In addition, we have shown that an H1N1 M2SR elicits protection against drifted H1N1 viruses in ferrets. Moreover, H1N1 M2SR provided protection against lethal H5N1 pandemic virus in ferrets. A prototype H3N2 M2SR vaccine, shown to be generally safe and well-tolerated in clinical trials and elicited immune responses in healthy adult subjects who were seronaive, seropositive and seroprotected. The H3N2 M2SR also provided protection against a highly drifted influenza virus in a human challenge trial. In this project, we propose to further develop M2SR as a quadrivalent (Quad) universal influenza vaccine that provides effective protection against drifted influenza viruses in the following specific aims: Aim 1a. Transfer of M2SR and BM2SR production platforms to US-based CMO. Aim 1b. Analytical method transfer, development and qualification at US-based CMO. These activities will accelerate development of the M2SR influenza vaccine toward a quadrivalent vaccine product that can provide broad cross-protection against drifted influenza viruses.