Scalable Manufacturing and Toxicity Testing of Intranasal M2SR Influenza Vaccine
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 U.S. and the rest of the world. Influenza virus infections circulate through human and animal populations year-round and while doing so they have a tendency to change over time. This tendency of the circulating virus to change is called antigenic drift. Occasionally, a new subtype of influenza virus to which the human population is unfamiliar will jump from infecting animals into infecting 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 animals to humans is called an antigenic shift. Influenza virus shifts were 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. Current vaccines have three or four virus components making them trivalent or quadrivalent vaccines, respectively. The components of the seasonal influenza vaccine change each year in order to match the predicted three or four drift viruses. Currently licensed influenza vaccines are modestly effective (50%-60%) at preventing influenza infection. However, in a year where the vaccine viruses and a 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 U.S. was calculated to only be 23% effective. In addition, seasonal influenza vaccines do not offer any protection against other 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, which is matched to the new virus subtype leaving the human population vulnerable to infection by the pandemic virus. 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 drifted seasonal viruses and shifted 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 based on an influenza virus that acts like a normal flu virus but is unable to produce an essential viral protein, M2. The vaccine virus is called M2SR. It 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 spreading the disease. Animal studies with the M2SR vaccine showed protection from drifted and shifted influenza virus infections suggesting that M2SR could be a universal influenza vaccine. More importantly, human clinical trials evaluating M2SR vaccine have shown that in addition to being generally safe and well-tolerated, the M2SR vaccine can protect against infection with an influenza virus that does not match the vaccine. For these trials, only one vaccine component was tested. Flu vaccines have four components. Therefore, as next steps in the development of the M2SR vaccine, FluGen optimized the manufacturing process used for the single-component M2SR vaccine, for cost-effective production of the other three components of the vaccine. This includes how the virus is grown and purified away from manufacturing debris. In this proposal, manufacture of M2SR at a large scale is proposed for use in a toxicology study so that clinical trials can be conducted with the Quadrivalent M2SR, the eventual product to be licensed. These proposed studies address Fiscal Year 2022 Peer Reviewed Medical Research Program Portfolio: Infectious Diseases, Respiratory Health; Topic Area: Viral Diseases and Respiratory Health; and Strategic Goal: Prevention. The capacity to manufacture all four components o
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310246
Entities
People
- Pamuk Bilsel
Organizations
- FluGen
- United States Army