COVID-19 Vaccine: Novel Intranasal Vaccine Platform Offers Opportunities For More Effective Vaccines With Lesser Side Effects
: Biotech and medical researchers from the University of Chicago and Duke University have created a new vaccine technology platform that allows the generation of the more effective vaccines with the fewest side effects using self-assembling peptide nanofibers tagged with antigens to prime the immune system against a potential invasion.
The research findings were published in the journal: Science Advances. https://advances.sciencemag.org/content/6/32/eaba0995
The finds showed that these nanofibers can induce an immune response and activate T cells without the use of additional adjuvants, which can induce inflammation and are associated with common vaccine side effects, like soreness at the injection site or low-grade fever.
Co-senior author Dr Anita Chong, Ph.D., a Professor of Surgery at the University of Chicago Medicine told Thailand Medical News, "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. 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."
It has been observed that the lining the surfaces of the lungs and intestines, dendritic cells act as a first point of contact for the innate immune system.
These dendritic 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.
The study cum development team 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.
Importantly, 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.
First author Dr Youhui Si, Ph.D., a research scientist at University of Chicago said, "The major advantage of subunit vaccines is safety since they don't involve the replication of live pathogens. On the other hand, to increase their effectiveness, subunit vaccines require adjuvants and repeated doses to induce long lasting immunity against a disease."
It has been known that adjuvants have the big downside of provoking inflammation.
Co-senior author Joel Collier, Ph.D., an Associate Professor of Biomedical Engineering at Duke University added, "This makes it difficult to find the balance between gett
ing a strong enough immune response and making the vaccine as safe and side effect-free as possible."
He further added, "The fiber the team developed is unique in that it does not require that inflammation.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 team says that not requiring adjuvants has a lot of advantages.
Dr Chong explained, "Aside from the inflammation issues, adjuvants require vaccines to be kept in cold storage. 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."
The study team believes that the primary strength of their nanofiber scaffolding is that it provides a physical structure that presents the antigens to the dendritic cells, making it easier for the innate immune system to recognize the antigens and begin a response.
Dr Chong further added, "I think there has not been enough attention toward understanding the physical scaffolding surrounding antigens, and the information that scaffolding provides to the immune system. This system will let us start picking apart the signals that are delivered by a physical structure; are they complimentary to, or distinct from, the soluble chemical adjuvants?"
Although the research was intended primarily to uncover the mechanism by which the nanofibers can induce an immune response, the results also demonstrate that this platform has great potential for generating safe, effective intranasal vaccines.
Dr Collier added, "We saw that the peptide fibers alone generated a strong immune response via the intranasal route. This route is great for vaccine compliance, because it doesn't involve a needle. Some people have a hard time with needles including myself! They can induce a vasovagal response, causing people to lose consciousness, and it's difficult to control. Eliminating needles from a vaccine platform could help with this issue and may mean that more people will seek out the vaccine."
This novel platform would also allow doctors and researchers to more precisely dial in the immune response to provide the best protection against a disease. They provided the example of SARS-CoV-2, the novel coronavirus that causes COVID-19, as an example where being able to fine-tune the immune response and delivering the vaccine directly to the most affected tissues could be beneficial.
Dr Collier added, "We do not know yet which antigens will be most maximally protective against COVID-19. This would let us very precisely target and produce antibodies and T cells that will provide the most protection."
The study team said that the intranasal platform and the similar sublingual platform, which involves spraying the vaccine under the tongue, have a lot of potential.
Dr Chong added, "Not only are these routes needle-free, making it easier and more comfortable for people to access, but they can also elicit an immune response in the lungs or mucosal tissues directly. Many infections occur through the oral and respiratory routes, including COVID-19, so being able to trigger that immune response in the right area of the body is very helpful, and could make a vaccine more protective."
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