The continuing COVID-19 pandemic is shining a shiny highlight on vaccine improvement. As quite a few vaccines race by means of medical trials, physicians and researchers proceed to work on growing new vaccine applied sciences to generate the best vaccines with the fewest unintended effects.
A brand new proof-of-concept examine by researchers on the College of Chicago and Duke College demonstrates the potential for one such platform, utilizing self-assembling peptide nanofibers tagged with antigens to prime the immune system towards a possible invasion.
Their analysis, revealed in Science Advances on August 7, 2020, confirmed that these nanofibers can induce an immune response and activate T cells with out the usage of further adjuvants, which might induce irritation and are related to frequent vaccine unintended effects, like soreness on the injection web site or low-grade fever.
“We wanted to understand how the body processed this nanofiber system, from its first interaction with the immune system to the point where it led to a complete immune response,” said co-senior author Anita Chong, Ph.D., a professor of surgery at the University of Chicago Medicine.
“In order to visualize the uptake of the nanofibers, we decided to try the intranasal route, because it would give us access to dendritic cells in the lungs and let us track their movement into the draining lymph nodes.”
Lining the surfaces of the lungs and intestines, dendritic cells act as a first point of contact for the innate immune system.
These cells bind to and gobble up the antigens found on the surface of invading pathogens, then turn around and present the antigens on their own cell surface to other immune system cells, including T and B cells.
This allows the T cells to initiate an immune response and prepare to defend the body against the invading bacteria, fungus or virus.
In the study, the researchers leveraged their nanofiber platform to test a specific kind of vaccine, called a subunit vaccine, which only uses a specific protein intended to act as the main antigen to stimulate an immune response.
This is in contrast to other kinds of vaccines, such as live-attenuated vaccines or inactivated vaccines, which challenge the immune system by introducing the whole virus, in a less virulent or inactive form.
Each type of vaccine has its advantages and disadvantages; live-attenuated vaccines can offer the most protection, but because they contain the actual pathogen, they frequently can’t be used for patients with weakened immune systems.
“The major advantage of subunit vaccines is safety since they don’t involve the replication of live pathogens,” said first author Youhui Si, Ph.D., a research scientist at UChicago. “On the other hand, to increase their effectiveness, subunit vaccines require adjuvants and repeated doses to induce long lasting immunity against a disease.”
Adjuvants have the big downside of provoking inflammation. “This makes it difficult to find the balance between getting a strong enough immune response and making the vaccine as safe and side effect-free as possible,” said co-senior author Joel Collier, Ph.D., an associate professor of biomedical engineering at Duke University.
“The fiber we’ve developed is unique in that it doesn’t require that inflammation,” he continued. “The scaffolding itself seems to be able to activate the dendritic cells to kick off the immune response. But before now, we didn’t have any real understanding of which pathways were involved in this process, so this study provides some insight into what’s going on.”
The researchers say that not requiring adjuvants has a lot of advantages. “Aside from the inflammation issues, adjuvants require vaccines to be kept in cold storage,” Chong said. “Without them, the peptides are quite heat stable, and can be delivered as a dry powder to be reconstituted into nanofibers on site, making it easier to get vaccines into resource-limited areas.”
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