New Yale study finds promising results with nasal COVID-19 vaccine
A team of Yale researchers recently published their findings that a nasal booster vaccine for COVID-19 may be a key way to help prevent the infection and transmission of COVID-19.
Regina Sung, Senior Photographer
A nasal booster vaccine could be key for preventing COVID-19 transmissions, according to a new study published by Yale researchers.
The research team — led by Benjamin Goldman-Israelow, a YSM assistant professor, and Tianyang Mao, a YSM graduate student — hopes to prevent the COVID-19 vaccine’s efficacy from waning over time with their nasal vaccine, called “Prime and Spike.” Immunity from the intranasal vaccine would build off of the initial vaccination to help produce mucosal immunity — immunity specifically located in the nose, respiratory tract and lungs.
The project is taking place in Sterling professor of immunobiology Akiko Iwasaki’s lab.
“[Prime and Spike] leverages the immune effector and memory responses that are created by the conventional vaccine and [redirects] it to the nasal mucosa,” Iwasaki said in a webinar hosted by the International Union of Immunological Societies. “This enables robust immune induction in the nasal cavity as well as in the lower respiratory tract … establishing tissue resonant memory cells.”
The nasal vaccine — which would be administered as a booster shot after an initial intramuscular vaccination — is a subunit vaccine, meaning it delivers a part of a COVID-19 spike protein to prime the body for infection.
This is where the name “Prime and Spike” comes from — the “prime” refers to the intramuscular vaccine “priming” the body for the “spike” protein delivered through the nasal vaccine.
In the study, researchers delivered 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 the controls and the mice that were not boosted with “Prime and Spike” were significantly more likely to become infected and die of infection.
While traditional intramuscular vaccines for COVID-19 have demonstrated effectiveness at preventing severe illness, current evidence indicates that efficacy of infection prevention wanes over time.
The researchers believe that the 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 could better protect against viral infection that enters within the respiratory tract, you will have a lower chance of breakthrough infection,” Goldman-Israelow said.“You could also have less shedding and less transmission of the virus.”
While “Prime and Spike” vaccine technology was first envisioned by the team to be used for a quicker responses to the next pandemic, the team realized that the vaccine could come into play during the current COVID-19 pandemic when it became clear that the mRNA vaccines had waning effectiveness in preventing infection.
The main reason why 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 that the intramuscular vaccines produce, according to Mao.
“The goal here is to be able to establish these front line cells that can immediately act upon and fight off infections when viruses first establish infection in the respiratory tissues,” Mao said. “[This is the] reason why we are developing a mucosal vaccine instead of a more typical vaccine approach that is delivered to establish systemic immunity.”
Currently, there is only one FDA approved intranasal vaccine for influenza. Mao noted that the reason why intranasal vaccines have been challenging to create is because there have been safety concerns with many of these vaccines.
Nasal vaccines typically utilize a live attenuated virus, or a weakened version of the virus that causes infection, and an adjuvant, which is a substance used to enhance immune response. However, some substances in adjuvants have been linked to negative and severe 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 administered after the intramuscular vaccine; pre-existing immunity is instead leveraged to act as an adjuvant. This increases the safety of the “Prime and Spike” vaccine compared to other nasal vaccines that have been tested.
In addition, 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 against different viral variants.
“Protein based manufacturing is something that the biotech field in general is very good at, in terms of producing them at mass and at high speed and adapting to new sequence configurations,” Mao said. “We need something that can be easily adaptable to the ever-evolving bio-variants and the newly emerging bio pathogens.”
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 can take approximately 6-12 months according to Goldman-Israelow. He said that if these studies go well, the “Prime and Spike” could go into clinical trials.
The “Prime and Spike” technology was patented by Yale and has been licensed to a start-up called Xanadu Bio. Iwasaki is one of the founders of Xanadu, and both Goldman-Israelow and Mao are currently serving 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 their work will set the foundation for the creation of nasal vaccines for other infections.
“With Sars-Cov-2, with the pandemic still being ongoing, I think that creates a lot of momentum,” Mao said. “I think we are in a really good place right now to push it forward and hopefully produce something that is translated into the clinic.”
As of November, according to the CDC, approximately 8% of Americans have received their updated COVID-19 booster shot.