Custom-designed nanoparticles key to new generation of highly
7 May 2009
Liquidia Technologies has developed a method to custom design and
produce nanoparticles for carrying vaccines that could provide more safe
and effective treatment for a wide variety of diseases.
A new study has shown that the desired immune response elicited by a
vaccine can be enhanced up to 10-fold when the vaccine protein is linked
to nanoparticles of a particular size and shape.
The discovery may lead to a new generation of vaccines that could
provide faster immunity to disease and potentially minimize the need for
multiple vaccinations or 'booster shots'.
“It has long been known that virus and bacteria come in a variety of
sizes and shapes and that the human body responds very differently to
each one of these disease-causing agents,” said Joseph DeSimone, Founder
of Liquidia Technologies and Chancellor’s Eminent Professor of Chemistry
at University of North Carolina — Chapel Hill.
“This data may help us better understand how to use the
characteristics of naturally occurring pathogens to create vaccines that
are more effective and require less product exposure for the patient.”
Current vaccination methods utilize weakened or deactivated pathogens
(disease causing agents) to elicit an immune response in the body
without the symptoms of the actual infection. Subsequently, if a person
is exposed to others with that particular disease their immune system
can quickly respond and more effectively fight off the infection.
This study suggests that an even greater immune response may be
generated when the same weakened pathogens are attached to
extraordinarily small particles that are well tolerated by the body.
“The immune system is very sensitive to the size and shape of foreign
bodies introduced into the body,” said Neal Fowler, CEO of Liquidia
Technologies. “Having insight into the role of these characteristics
when mounting an immune response is a very significant step toward
finding safer and more effective ways of administering vaccines to
The particles used in this study were created using a proprietary
method known as PRINT, which stands for Particle Replication In
Non-wetting Templates. The PRINT Platform leverages the precision of
micro-electronics to create rationally designed nanoparticles with
absolute control over particle size, shape, composition and surface
chemistry in a controlled and scalable manufacturing process.
In developing particle technologies for vaccines, each of these
variables can be optimized for a specific immunogenic response allowing
for an unprecedented level of design control compared to other delivery
systems. In addition to controlled co-delivery of antigens or other
pharmacological agents that can increase or aid their effect, the PRINT
platform allows the exploration of the impact of non-spherical particle
shapes on biological response.
About the study
Immunogenicity studies were performed with a variety of cross-linked
polyethylene glycol particles of different sizes and shapes produced
using PRINT technology.
The effect of particle size on a monovalent vaccine was performed
using the Wyoming/3/2003 H3N2 influenza A protein, which was then
attached to the surface of these particles. Two micrograms of the
protein associated particles was injected into BALB/c mice, and antibody
response was monitored using an Enzyme-Linked Immunosorbent Assay
(ELISA). Soluble Wyoming/3/2003 H3N2 influenza A protein was used as a
At 5 weeks post injection, it is found that microparticles with
higher aspect ratios (ratio of its longer dimension to its shorter
dimension) have significantly higher antibody titers than particles with
an aspect ratio of 1 or soluble protein. It was found that particles
with a long axis of 10 micrometers did not inhibit the evolution of a
strong immune response with the 1 x 10 x 1 micrometer particle.
An adjuvant effect was also observed with a high aspect ratio 80 x
360 nm particle using the Novartis Fluvirin™ trivalent influenza
vaccine. This vaccine contains equivalent amounts of A/Brisbane/59/2007
(H1N1), A/Uruguay/716/2007 (H3N2), and B/Florida/4/2006. Immunogenicity
studies were performed with 80 x 360 nm particles. BALB/c mice were
injected with 1 microgram of total protein (0.33 microgram each), and
antibody response was monitored by ELISA. Injections were performed at
days 0 and 21.
After a single injection, the particle delivery of the vaccine
proteins provided a 10-fold increase in antibody titer over the
injection of the vaccine product alone. After a second injection, the
antibody titers increase significantly. The trends remain similar to the
initial injection with particles showing a 10-fold increase over the
soluble vaccine product.
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