Novel Adjuvant for Increasing Effectiveness of Vaccines
NJH ID: #10-13
Background
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.
Technology
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 for
patient use, with a viral nuclear protein can maintain long-lived memory CD8 T
cells and protect mice from influenza viral challenge.
Potential Applications
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.
Publication
Vaccine adjuvants aluminum and monophosphoryl lipid A provide distinct signals to generate protective cytotoxic memory CD8 T cells McLeod, MK et al. PNAS May 10, 2011 vol. 108 no. 19 7914-7919.
Patent Status
US patent pending. Published international patent WO 2011/057267.
Inventors
John W. Kappler Ph.D., Philippa Marrack Ph.D., Meghan MacLeod, Ph.D., Amy McKee
Licensing Status
This technology is available for licensing.
For Further Information, Contact:
Emmanuel Hilaire, PhD
Manager
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: 303.398.1262
Fax: 303.270.2352
HilaireE@njhealth.org
