Pulendran, Ph.D., study leader and Charles Howard Candler professor of
pathology and laboratory medicine at Emory University School of Medicine, along
with Sudhir Pai Kasturi, Ph.D., co-author of the study who works in Pulendran's
lab, and Niren Murthy, Ph.D., co-author and associate professor in the Wallace
H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory
University, have found the key to long-lasting immunity through the use virus-mimicking
yellow fever vaccine is one of the most long-lasting vaccines, protecting humans against the virus for
decades with just one injection. Nobel Prize winner Max Theiler developed it in
the 1930's, and scientists have been looking to imitate and improve upon this
team of researchers from Emory has created nanoparticles, which are made of
biodegradable polymers, which are similar to viruses in immunological composition
and size, which has led to lifelong immunity in mice. More specifically, the
nanoparticles are made of PLGA - poly(lactic acid)-co-(glycolic acid) and their
two main components are MPL (monophophoryl A) and imiquimod. These
nanoparticles can be used interchangeably with material from a variety of
viruses or bacteria.
results address a long-standing puzzle in vaccinology: How do successful
vaccines induce long-lasting immunity?" said Pulendran. "These
particles could provide an instant way to stretch scarce supplies when access
to viral material is limited, such as pandemic flu or during an emerging
infection. In addition, there are many diseases, such as HIV, malaria,
tuberculosis and dengue that still lack effective vaccines, where we anticipate
that this type of immunity enhancer could play a role."
nanoparticles are able to provide lifelong immunity by activating two separate
areas of the innate immune system. This is similar to how the yellow fever
vaccine works, which stimulates Toll-like receptors (TLRs) in the innate immune
system. TLRs are molecules that are capable of sensing "bits" of viruses,
parasites and bacteria and are expressed by cells.
are like the sixth sense in our bodies, because they have an exquisite capacity
to sense viruses and bacteria, and convey this information to stimulate the
immune response," said Pulendran. "We found that to get the best
immune response, you need to hit more than one kind of Toll-like receptor. Our
aim was to create a synthetic particle that accomplishes this task."
demonstrated that the yellow fever vaccine was sensed by the immune system
through several TLRs, and that this was key to immunity through the use of the
nanoparticles. Mouse models showed that the nanoparticles boosted production of
antibodies to proteins from anthrax bacteria or flu virus much more effectively
than alum, which was the only FDA-approved vaccine additive for decades. Also,
the immune cells provided protection in the lymph nodes of the mouse for almost
the entire lifetime of a mouse, which is about 18 months.
are very excited about building on this platform to design improved vaccines
for existing and emerging infectious diseases," said Kasturi.
This study was published in Nature.