New Yale study finds promising results with nasal COVID-19 vaccine

New Yale study finds promising results with nasal COVID-19 vaccine

Regina Sung, Senior Photographer

A nasal booster vaccine could be key to preventing COVID-19 transmissions, according to a new study published by Yale researchers.

The research team, led by Benjamin Goldman-Israelow, an assistant professor at YSM, and Tianyang Mao, a YSM graduate student, hopes to prevent the effectiveness of the COVID-19 vaccine from waning over time with their nasal vaccine, called “Prime and Spike”. Immunity from the intranasal vaccine would build on the initial vaccination to help produce mucosal immunity, immunity located specifically in the nose, respiratory tract, and lungs.

The project is taking place in the lab of Sterling immunobiology professor Akiko Iwasaki.

“[Prime and Spike] harnesses the immune effector and memory responses created by the conventional vaccine and [redirects] to the nasal mucosa,” Iwasaki said at a webinar hosted by the International Union of Immunological Societies. “This allows for robust immune induction in the nasal cavity as well as the lower respiratory tract… establishing resonant memory cells in the tissues.”

The nasal vaccine, which would be given as a booster injection after an initial intramuscular vaccination, is a subunit vaccine, meaning it delivers a part of a COVID-19 spike protein to prepare the body for infection.

This is where the name “Prime and Spike” comes from: “prime” refers to the intramuscular vaccine that “prepares” the body for the “spike” protein that is administered through the nasal vaccine.

In the to study, the researchers administered the nasal vaccine to both mice and hamsters. The control group received no vaccine, one group received only the intramuscular vaccine, and the last group received both the intramuscular vaccine and the nasal booster. When exposed to the COVID-19 virus, all controls and mice that were not boosted with “Prime and Spike” were much more likely to become infected and die from the infection.

While traditional intramuscular vaccines for COVID-19 have proven effective in preventing serious illness, current evidence indicates that the effectiveness of infection prevention decreases over time.

The researchers believe that mucosal immunity induced by the nasal vaccine was the key to preventing infection in the Prime and Spike-boosted mice.

“The hypothetical benefit of creating tissue-specific immunity is that [if] You might be better protected against viral infection that gets into your respiratory tract, you’ll have a lower chance of advanced infection,” Goldman-Israelow said. “You could also have less spread and transmission of the virus.”

While the team first envisioned “Prime and Spike” vaccine technology being used for faster response to the next pandemic, the team realized the vaccine could come into play during the current COVID-19 pandemic. 19 when it became clear that mRNA vaccines had diminishing efficacy in preventing infection.

The main reason mucosal immunity would be key to preventing infection is that the respiratory system can respond more quickly to infection than circulating antibodies and T cells produced by intramuscular vaccines, according to Mao.

“The goal here is to be able to establish these front-line cells that can immediately act and fight infections when viruses first establish infection in respiratory tissues,” Mao said. “[This is the] which is why we are developing a mucosal vaccine rather than a more typical vaccine approach that is administered to establish systemic immunity.”

Currently, there is only one FDA-approved intranasal influenza vaccine. Mao noted that the reason intranasal vaccines have been difficult to create is because there have been safety issues with many of these vaccines.

Nasal vaccines typically use a live, attenuated virus, or a weakened version of the virus causing the infection, and an adjuvant, which is a substance used to enhance the immune response. However, some adjuvant substances have been linked to serious negative side effects, such as Bell’s palsy — partial facial paralysis.

The researchers found that the use of an adjuvant can be avoided if the nasal vaccine is given after the intramuscular vaccine; instead, pre-existing immunity is harnessed to act as an adjuvant. This increases the safety of the “Prime and Spike” vaccine compared to other nasal vaccines that have been tested.

Furthermore, Mao noted that one of the other advantages of the “Prime and Spike” vaccine is its ability to be quickly and easily modified to fight different viral variants.

“Protein-based manufacturing is something that the biotech field in general is very good at, in terms of mass-producing them at high speed and adapting to new sequence configurations,” Mao said. “We need something that can easily adapt to constantly evolving biovariants and new emerging biopathogens.”

While the “Prime and Spike” vaccine has shown promising results in both mice and hamsters, the next step would be to test the efficacy and non-toxicity of the vaccine in non-human primates, which may take approximately 6-12 months depending on Goldman-Israelow. He said that if these studies go well, “Prime and Spike” could enter clinical trials.

The “Prime and Spike” technology was patented by Yale and has been licensed to a new company called Xanadu Bio. Iwasaki is one of the founders of Xanadu, and both Goldman-Israelow and Mao currently serve as consultants.

Goldman-Israelow believes that, if all goes well, the “Prime and Spike” vaccine could serve as a COVID-19 booster for years to come. In addition, the team hopes that their work lays the groundwork for creating nasal vaccines for other infections.

“With Sars-Cov-2, with the pandemic still going on, I think that creates a lot of momentum,” Mao said. “I think we’re in a very good place right now to push it forward and hopefully produce something that translates to the clinic.”

As of November, according to the CDC, about 8% of Americans have received their updated COVID-19 booster shot.

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