GMP Production of Candidate Pan-Group 2 Influenza A Virus Vaccines
Abstract
Seasonal influenza virus infections are a significant public health burden causing 250,000 to 500,000 deaths per year globally. Vaccines are available and effective if well matched with the circulating strains, called H1N1 and H3N2. However, influenza viruses constantly change their surfaces to escape immunity and therefore the vaccine has to be adjusted to new strains and readministered every year. The strain selection for the vaccine of the next season is based on predictions and wrong strains are selected on a regular basis causing suboptimal vaccine protection. In addition, influenza viruses cause pandemics in irregular intervals, which can result in up to 50 million deaths. These pandemics are usually caused by spillover of avian influenza viruses (bird flu) that have drastically different surfaces. A wide variety of these different viruses circulate in wild birds, which are the natural reservoir of influenza viruses. Seasonal vaccines do not protect against these novel viruses (for instance, the bird flu strain H5N1) and a matched vaccine has to be manufactured, a process that takes 6 months and leaves the population vulnerable in the meantime. While current vaccines target parts of the virus that the virus can easily change, novel vaccine strategies have been designed by our group to target more conserved regions. Immunity towards one of these regions, the stalk domain of the viral surface protein hemagglutinin, is highly and broadly protective against ever-changing seasonal as well as novel pandemic influenza viruses. This part of the virus is conserved within phylogenetic group 1 viruses like seasonal H1N1 and the avian H5N1 influenza virus as well as within group 2 viruses like human H3N2 and avian H7N9 viruses. Our group has designed a vaccine that provides protection against all group 1 influenza viruses (including various strains of bird flu) by inducing more immunity toward this conserved area, and our vaccine has been successfully advanced into two different Phase I clinical trials. However, group 2 viruses like seasonal H3N2 and avian H7N9 strains cause significant problems in humans and are not targeted by this vaccine. To create a truly universal influenza virus vaccine, both a group 1 component as well as a group 2 component are urgently needed. Here we propose to develop a vaccine that provides broad protection from influenza infections caused by group 2 viruses like H3N2 and H7N9 based on the conserved stalk domain of the hemagglutinin. The vaccine concept will be similar to the concept developed for group 1 viruses, which will be used as a blueprint to success. A vaccine will be designed and produced in a quality suitable for clinical testing. The products will be tested in two animal models as well as in formal toxicology tests. At the end of this project, we will have product and required data in place to transition into clinical testing. Ultimately, this product can be combined with the already developed group 1 product. Having a universal influenza virus vaccine that provides protection against all influenza A viruses (group 1 and group 2) will abolish the need for annual reformulation and readministration of the vaccine, will significantly enhance our pandemic preparedness, and will save millions of lives.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810488
Entities
People
- Florian Krammer
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army