Safety and Immunogenicity of H3N2 M2SR Monovalent Influenza Vaccine Administered with Inactivated Flu Vaccine in Older Subjects
Abstract
Influenza viruses cause a respiratory disease resulting in over 200,000 hospitalizations and ~ 36,000 deaths per year in the U.S. Older adults, over the age of 65, exhibit increased susceptibility to influenza viruses, accounting for 90% of annual influenza-related fatalities. Vaccination remains the primary method of influenza prevention, but alterations in immune function with age result in impaired vaccine responses, with estimates of efficacy as low as 9% in healthy older adults and even lower in older adults with underlying chronic diseases who are at risk for disability, hospitalization, and death. For H3N2 influenza strains, the vaccine effectiveness in the >65 year-old age group is even lower. The influenza vaccination program is an essential component of the Department of Veterans Affairs (VA) health promotion and disease prevention programs. The Veterans Health Administration (VHA) has made influenza vaccination a priority. Multiple DOD studies have indicated that the current vaccines provide only low to moderate protection against influenza. Even with the advent of newer influenza vaccines targeted specifically at the elderly (Fluzone High Dose/Fluad), there remains an urgent need to prepare influenza vaccines that can provide those over 65 in the U.S. and the world with better efficacy. The goal of FluGen’s novel M2SR influenza vaccine is to provide a cost-effective, rapidly manufactured influenza vaccine that demonstrates superior efficacy in all age groups, including the elderly, by providing broad spectrum immunity. Two human clinical trials evaluating the intranasally delivered M2SR vaccine have been conducted to date. A human challenge study demonstrated that subjects immunized with the M2SR vaccine are protected against a drifted influenza virus. A dose-ranging study has shown high serum antibody levels that are not seen with the currently licensed intranasal live vaccine, FluMist. In this proposal, we will explore the ability of a novel investigational influenza vaccine M2SR to stimulate immune responses in older subjects. This proposed human clinical study to test M2SR to protect subjects primarily addresses FY20 PRMRP Topic Area of Respiratory Health. FluGen has designed a new vaccine, called M2SR, based on an influenza virus that is unable to produce the essential M2 protein. The M2SR virus is able to infect cells but cannot spread from cell-to-cell or person-to-person, thus helping to build immunity against influenza but not spread the disease. Animal studies with the M2SR vaccine showed that they were protected from drift and shift influenza virus infection suggesting M2SR could be an effective influenza vaccine against multiple influenza viruses. Successful demonstration that the M2SR vaccine is able to generate immune responses in older individuals will demonstrate that it is a leading influenza vaccine candidate and help it to move rapidly through development and toward U.S. Food and Drug Administration approval. Approval of a more effective, broadly protective vaccine such as M2SR will have tremendous public health benefits. Seasonal influenza kills tens of thousands of Americans annually with the very young and the elderly being the most affected. In addition, seasonal influenza infections cause a significant loss of productivity and hospitalization costing the U.S. economy billions of dollars. Influenza also has a devastating effect on readiness of our Warfighters because it can rapidly spread through units causing significant illness requiring medical attention. Finally, a universal M2SR could save hundreds of thousands to millions of lives by preventing or blunting the emergence of the next influenza pandemic by creating immunity in the population so that people exposed to a new virus subtype already have existing immunity to it.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110563
Entities
People
- Pamuk Bilsel
Organizations
- FluGen
- United States Army