Color-enhanced scanning electron micrograph shows splenic tissue from a monkey with inhalational anthrax; featured are rod-shaped bacilli (yellow) and an erythrocyte (red). Image: Arthur Friedlander |
Lawrence Livermore National Laboratory,
working with Loyola
University, has won a
$3.5 million grant from the National Institutes of Health to help develop a new
anthrax vaccine. The grant is the first major NIH-funded biodefense grant
focused on LLNL’s nanolipoprotein technology.
Nanolipoprotein (NLP) technology is a
potential breakthrough in vaccine development. Today, many vaccines are based
on a single protein derived from a specific pathogen (bacterial, viral,
fungal). The idea is that the body “sees” the protein as foreign and
mounts an immune response to kill the invader, which keeps the body free from
disease.
However, this approach to vaccine design
has not been as effective as whole organism vaccines in protecting people from
getting sick. NLP technology, pioneered by Lab scientists Paul Hoeprich, Matt
Colman, Nick Fischer, and Craig Blanchette has the potential to revolutionize
vaccine design, constituting a novel next-generation vaccine that can more
readily prevent disease and better protect people.
To achieve this, the scientific team has
developed methods to mix NLPs with specific pathogen-derived proteins. After
the NLP and the proteins are mixed, the proteins anchor to the surface of the
NLP.
Effectively, the NLP provides a delivery
platform for the proteins of interest, and it is this construct that has been
used successfully as a vaccine in mice.
Under Hoeprich’s direction, Fischer,
Blanchette, and other scientists have used NLPs to create a successful vaccine
against West Nile Virus. These experiments led to some key observations
regarding the NLPs:
- NLPs provide a flexible platform for vaccine
formulation. - Vaccines based on NLPs can be easily adjusted to either
better meet a need or meet a slightly different need. - NLP-based vaccines are potentially more robust and can
be freeze-dried, meaning unlike first-generation vaccines, they may not
need refrigeration and/or require special handling. - NLP vaccines can be administered by non-invasive
methods such as intra-nasally, similar to the FluMist vaccine.
Based on this large body of NLP-related
work, LLNL has secured a series of patents to protect the intellectual property
resulting from the NLP team’s inventions. “The NLP will become a platform
for an entire new generation of treatments,” Hoeprich says. “The NLP
will be like an operating system, and a wide range and variety of applications
can be built for it.”
The Lab’s share of the grant will come to
about $2.5 million during the five-year period and will help support a team of
approximately six scientists, many of whom have spent years pioneering NLP
technology, says Amy Rasley, the LLNL biomedical scientist who co-authored the
proposal along with Hoeprich and Adam Driks of Loyola University. And,
according to Rasley, the new project fits nicely into LLNL’s broader efforts to
pursue NLPs for a variety of novel research applications.
“Winning this grant is a direct
result of the Lab identifying and nurturing our NLP technology and building the
infrastructure to support the research. LLNL is the only Department of Energy
facility with a BioSafety Level 3 lab,” Hoeprich says. “This
investment is paying off with the NIH grant and five other NLP projects are
under way…and we’re just getting started.”
“I spent most of my career working
for pharmaceutical companies,” says Hoeprich. “Working at the Lab is
like a dream come true for me because I’ve been able to come up with some
interesting ideas and do the science necessary to turn them into tools that can
impact global health, especially in under-developed countries.”