Scientists at Oregon State
University have developed a new "adjuvant" that could allow the
creation of important new vaccines, possibly become a universal vaccine carrier
and help medical experts tackle many diseases more effectively.
Adjuvants are substances that are not immunogenic themselves, but increase
the immune response when used in combination with a vaccine.
However, due to concerns about safety and toxicity, there's only a single vaccine
adjuvant – aluminum hydroxide, or alum – that has been approved
for human use in the United States. It's found in such common vaccines as hepatitis
B and tetanus. But even though widely used, alum is comparatively weak and will
only work with certain diseases.
The new adjuvant is based on nanoparticles prepared with lecithin, a common
food product. In animal models, it helped protein antigens to induce an immune
response more than six times stronger than when alum was used. Researchers also
showed that the lecithin nanoparticles were able to help induce a reasonable
antibody response after only one shot, whereas it took at least two shots for
the alum adjuvant to work.
Based on their studies, researchers believe the lecithin nanoparticles have
wide potential applications and possibly a good safety profile. Their findings
were just published in the Journal of Controlled Release, a professional journal
in the field of pharmaceutics, in work supported by the National Institute of
Allergy and Infectious Diseases.
"In many cases, to make progress with vaccine development we need new
adjuvants," said Zhengrong Cui, an assistant professor of pharmaceutics
at OSU and corresponding author on the new study. "The material has to
be safe, and lecithin is a common food product that's already widely used in
pharmaceuticals. This new form of using lecithin nanoparticles as an adjuvant
is promising and could become very important."
Vaccine development has always been difficult and at times controversial, Cui
said, because of concerns about adverse effects when giving vaccines to healthy
people.
Because of that, the U.S. Food and Drug Administration has been conservative
about approving new vaccine adjuvants, he said. But even the safety issue is
complex – to help avoid risk, new vaccines are based on purified compounds
from microbes, but these provoke a very weak immune response and often need
an adjuvant to boost them. Vaccines could be made based on dead or live attenuated
microbes, but that would have a higher level of risk. The ultimate solution
is new and improved adjuvants that help address both concerns about safety and
efficacy.
Another problem, he said, is that the alum adjuvant that is common in some
U.S. vaccines has very limited value in the development of many potential vaccines
against viruses or tumors.
By contrast, the lecithin-based nanoparticle adjuvant is more effective. The
extraordinarily small particles move easily to the lymphatic system that plays
a key role in development of immune response, and they physically "look
like" a pathogen to the immune system, which quickly gears up to fight
them.
"Our early studies with laboratory animals seem to suggest that a vaccine
based on the lecithin nanoparticle adjuvant would not only be more effective,
but be tolerated by the body more readily than one using alum," Cui said.
"Lecithin is very non-toxic, it's one of many compounds 'generally recognized
as safe' by the FDA, and at the injection site we saw none of the nodules and
tissue hardening you sometimes see with vaccines that use alum."
If the new adjuvant is ultimately shown to be safe and is approved following
clinical trials, Cui said, it could become the basis for a revolution in the
production of vaccines and serve as a universal carrier.
Posted September 14th, 2009
