Intranasal Vaccine Platform May Be More Effective for COVID-19 Vaccine With Fewer Adverse Effects


Intranasal vaccine platform may allow for an immune response to be induced more precisely to provide the best possible protection from coronavirus disease 2019.

An intranasal vaccine platform may have the potential to be more effective for vaccine delivery with fewer adverse effects (AEs), according to research published in Science Advances.

With the ongoing coronavirus disease 2019 (COVID-19) pandemic still affecting the world, researchers have been racing to develop the most effective vaccines with the fewest AEs. The University of Chicago and Duke University have collaborated on a new proof-of-concept study that shows the potential for using self-assembling peptide nanofibers tagged with antigens that ready the immune system for a potential attack.

The nanofibers are able to induce an immune response and activate T cells without additional adjuvants. The additional adjuvants have shown the potential to induce inflammation and other common vaccine AEs, such as soreness at the injection site or low-grade fever, according to the study.

"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, PhD, a professor of surgery at the University of Chicago Medicine, in a press release. "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."

The dendritic cells line the surfaces of both the lungs and intestines, and act as a point of initial contact for the innate immune system. The cells then adhere to and absorb the antigens superficially present on the invading pathogens and then present those same antigens on their own surface to other cells in the immune system, including T and B cells. This then supports the T cells’ initiation of a response to defend against the invading bacteria, fungus, or virus, the study noted.

According to the researchers, the subunit vaccine, in particular, is effective for this because it uses a specific protein that acts as the antigen in the stimulation of an immune response. Other vaccines instead introduce the whole virus, such as live-attenuated vaccines or inactivated vaccines; however, such vaccines become more of a challenge to the immune system.

For example, although live-attenuated vaccines can offer the most protection because they contain the actual pathogen, these vaccines frequently can't be used for patients with weakened immune systems. Yet, subunit vaccines also have disadvantages, as they require adjuvants and repeated doses to induce long lasting immunity, according to the researchers.

"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, PhD, an associate professor of biomedical engineering at Duke University, in the press release.

However, the fiber developed by the researchers is unique in that it doesn’t require inflammation.

“The scaffolding itself seems to be able to activate the dendritic cells to kick off the immune response,” Collier explained. “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."

Other than the inflammation that it requires, adjuvants also have the downside of needing to be kept in cold storage, the researchers noted. However, without the addition of adjuvants, peptides are heat stable and can be delivered in a dry powder form. In this form, they can later be reconstituted into nanofibers at the administration site, making it much easier to provide vaccines to resource-limited areas, according to the study.

Although the researchers’ original intention was to investigate the mechanism that allows the nanofibers to induce an immune response, they also observed that the platform has potential as a way to generate safe, effective intranasal vaccines.

"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," Collier said. "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."

Additionally, the intranasal platform may allow for the immune response to be induced more precisely to provide the best possible protection from disease. For example, fine-tuning the immune response and delivering the vaccine directly to the most affected tissues may be beneficial with severe acute respiratory syndrome coronavirus 2, the novel coronavirus that causes COVID-19.

"We don't know yet which antigens will be most maximally protective against COVID-19," Collier said. "This would let us very precisely target and produce antibodies and T cells that will provide the most protection."

The researchers also noted that the sublingual platform, which delivers the vaccine by spraying under the tongue, also has a lot of potential.

"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," Chong said. "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."


Intranasal vaccine platform has potential for more effective vaccines, fewer side effects. Chicago, IL: University of Chicago Medical Center; August 7, 2020. Accessed August 10, 2020.

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