NJH ID: #10-13
Most current vaccines, including those against influenza, act via the generation of specific antibodies that can either neutralize or otherwise inactivate the pathogen. These vaccines induce the production of antibodies against viral surface proteins to prevent viral cellular entry. However, as far as influenza is concerned, these viral surface proteins tend to mutate over time and as a result a new vaccine against influenza must be developed every year. To avoid this problem, the ideal vaccine would be pan-specific across strains of influenza virus.
Targeting CD8 T cell mediated immunity could be the right strategy to reach this goal. The portions of influenza virus that are recognized by cytotoxic CD8 T cells are much less variable than those recognized by antibodies. Thus a vaccine designed to activate CD8 T cells has the potential to protect against yearly and newly emerging pandemic viral subtypes.
Dr. Marrack’s laboratory at National Jewish Health has discovered how to prime a second arm of the immune system to boost the effectiveness of influenza vaccines. They demonstrated that the combination of two adjuvants (alum and monophosphoryl lipid A, MPL), already approved f3or patient use, with a viral nuclear protein can maintain long-lived memory CD8 T cells and protect mice from influenza viral challenge.
A combination of two adjuvants, such as alum and MPL, with an internal viral protein can be used to induce CD8, (killer) T cells to join antibodies in response to viral infection. CD8 T cell epitopes are much less variable and thus a vaccine designed to activate protective CD8 T cells has the potential to protect against yearly and newly emerging pandemic viral subtypes. This new approach could be applicable to infectious disease such as the flu and malaria.
State of Development
Investigators have tested the combination of adjuvants (alum and MPL) in a mice model of Influenza A infection. Mice primed with nucleoprotein of influenza A (NP) and both adjuvant lost less weight and quickly regained their original weight in contrast to mice primed with NP/protein and either adjuvant.
Macleod, M. K. L., A. S. Mckee, A. David, J. Wang, R. Mason, J. W. Kappler, and P. Marrack. "Vaccine Adjuvants Aluminum and Monophosphoryl Lipid A Provide Distinct Signals to Generate Protective Cytotoxic Memory CD8 T Cells."Proceedings of the National Academy of Sciences 108.19 (2011): 7914-919. PMID: 21518876.
US patent pending. Published US Application US-2016-0175431-A1. Published international patent WO 2011/057267.
John W. Kappler Ph.D., Philippa Marrack Ph.D., Meghan MacLeod, Ph.D., Amy McKee
This technology is available for licensing.
For Further Information, Contact:
Emmanuel Hilaire, PhD
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206