A Randomized, Placebo-Controlled Phase 2a Study in Healthy Volunteers to Evaluate the Cross-Protective Efficacy of M2SR in an Influenza Challenge Model
Abstract
Seasonal influenza virus infections are one of the most serious respiratory infections, causing significant annual illness, hospitalizations, loss of life, and productivity, in the US and the rest of the world. Influenza virus infections circulate through human and animal populations year-round, and as they circulate through these populations they have a tendency to change over time. This tendency of the circulating virus to change is called drift. Occasionally, a new subtype of influenza virus with which the human population is unfamiliar will jump from circulation in animals into circulation in man. When this happens, and this new virus starts to circulate rapidly and widely, it can cause an influenza pandemic. This new subtype jump from animal circulation into the human population circulation is called a shift. An influenza virus shift was responsible for the four influenza pandemics that occurred in the last century. The primary way to protect against influenza infection is through use of the seasonal influenza vaccine. The seasonal influenza vaccine changes each year in order to “match” the predicted drift virus. Currently licensed influenza vaccines are modestly effective (50%-60%) at preventing influenza infection. However, in a year in which the vaccine and the circulating drifted virus do not match, the effectiveness can be much less. For example, during the 2014-2015 influenza season, the vaccine used in the US was calculated to be only 23% effective. In addition, seasonal influenza vaccines do not offer any protection against other novel subtypes that can shift circulation into the human population and cause an influenza pandemic. When a shift like this happens, it can take up to 6 months to make a new vaccine that is matched to the new virus subtype. There is a clear need for better influenza vaccines to prevent seasonal influenza infections and to provide protection against a virus shift that could result in an influenza pandemic. An influenza vaccine that protects against drift seasonal viruses and shift viruses would be considered a universal influenza vaccine because it would offer protection against all types of influenza infection. 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 a universal influenza vaccine. Human clinical trials evaluating the M2SR vaccine are currently underway. As a next step in the development of the M2SR vaccine, FluGen proposes to do a set of human influenza challenge studies to demonstrate that subjects immunized with the M2SR vaccine are protected against drift and shift influenza virus. In addition, samples from the subjects in this study will be analyzed to determine if there are markers to indicate if a subject is immune to influenza. These proposed human challenge studies to test M2SR to protect subjects primarily address Fiscal Year 2016 Peer Reviewed Medical Research Program Area of Encouragement for Influenza, “Development and testing of a universal influenza vaccine.” Secondarily, analysis of these clinical studies will shed light on an additional Areas of Encouragement, “Research to improve understanding of host responses to influenza infection.” Successful demonstration that the M2SR vaccine is able to protect human subjects from a challenge with drift and shift influenza viruses will demonstrate that it is a leading universal influenza vaccine candidate and help it to move rapidly through development and toward Food and Drug Administration approval. Approval of a universal M2SR vaccine will have tremendous public health benefits. Seasonal influenza kil
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710430
Entities
People
- Pamuk Bilsel
Organizations
- FluGen
- United States Army