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Nanoparticles used to provide lifelong immunity in mice. The blue area represents resting B cells, the red area represents activated B cells being trained to create antibodies and the green area represents specialized antibody producing cells.
Nanoparticles activate two areas of the innate immune system, stimulating Toll-like receptors and providing lifelong immune protection in mice

Bali 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 nanoparticles.

The 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 design.

Now, the 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.

"These 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." 

The 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.  

"TLRS 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." 

The team 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. 

"We 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.





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