Cate Roser

Researchers at the Yale School of Medicine published a study suggesting that nasal vaccines can provide robust immunity against COVID-19 and other similar respiratory viruses. 

Tianyang Mao, a fifth year doctoral immunology student at the medical school, and Benjamin Israelow, an infectious disease fellow at the medical school, are the co-first authors of the study. They work within the laboratory of Akiko Iwasaki, professor of immunobiology and molecular, cellular and developmental biology. The article was published as a pre-print on Jan. 26 and shows that, in subjects vaccinated with the Pfizer mRNA vaccine against COVID-19, the nasal vaccine elicited an immune response in the mucosal membranes of the body, which could potentially prevent the virus from infecting and replicating within a host body. 

“[In the study] we show that nasal booster vaccine using unadjuvanted spike protein after conventional intramuscular mRNA vaccine induces robust mucosal immune responses, including IgA, memory B and T cell responses that reside within the nasal and lung cavities,” Iwasaki wrote to the News. “IgA is able to capture the virus before it contacts the host cells. Memory B and T cells can be quickly restimulated to provide local immune defense, at the site of viral exposure, the nose and throat.”

Mao explained that the nasal vaccines were developed to address a weakness observed with the current COVID-19 vaccines: While these mRNA vaccines are incredibly effective at preventing severe illness and hospitalization, they are less effective at preventing infection and transmission.

According to Israelow, it is important to distinguish between two types of antibodies. The common vaccines against COVID-19, specifically Pfizer’s mRNA vaccine, trigger the creation of systemic antibodies, which circulate within the blood and prevent severe illness. These antibodies, called IgG, are Y-shaped and attack the virus once the host has been infected. 

The mucosal vaccine, when used in tandem with Pfizer’s vaccine, triggers the production of secreted IgA antibodies. These antibodies reside within the mucosal lining of the respiratory tract and are in the shape of two Y’s that are fused together.

“Essentially, they are sitting there ready to bind to a pathogen.” Israelow said. “IgA antibodies reside pretty much outside of our bodies. By inducing [the production of IgA], our thought is that we can prevent infection.”

In other words, the nasal vaccine developed by Yale researchers worked in tandem with the Pfizer vaccine to create antibodies that attack the virus at the very beginning of infection, when it is still in the respiratory tract, neutralizing the pathogen and preventing it from replicating. The hope is that this approach will decrease the incidence of infections even after exposure to COVID-19. 

In the study, researchers primed the test animals with the Pfizer vaccine and then boosted them intranasally with the SARS-CoV-2 spike protein. This technique, called “prime and spike,” triggers COVID-19 immunity to expand from systemic immunity to mucosal immunity, according to Israelow. 

“In order for an immune response to occur within the mucosal tissue — and this may apply differently to different mucosal tissues — generally speaking you need either cognate antigens and/or some sort of pro-inflammatory signals that are provided locally to recruit circulating T and B cells to be physically present within the mucosal tissues.” Mao said. 

The goal is to create a signal within the mucosal membrane that will alert the immune system that a response is needed in the respiratory tract. The characteristics of the immune response that are subsequently triggered may vary depending on the location and type of mucosal tissue, according to Mao. 

This new study builds upon previous work on intranasal vaccinations conducted in Iwasaki’s laboratory. Last December, Iwasaki published a paper in Science Immunology which showed that intranasal boosters for influenza “enhanced antiviral immunity and IgA production when administered intranasally rather than by alternate parenteral routes.”

The research to translate Iwasaki’s previous research on influenza nasal vaccination to COVID-19 began before the onset of the Omicron variant, according to Israelow. However, he recognized that the emergence of Omicron highlights the “pressing need” for an intranasal or mucosal vaccine. 

Mao added that the preprint study only considers testing animals, and it is a preclinical study. However, he added that the laboratory is working to continue investigating these nasal vaccines. 

“We would love to be able to move this onto more animal models that better mimic the human immune system,” Mao said. “We are thinking of testing our strategies in non-human primates because they have similar immune systems and develop similar immune responses to humans. We are also enthusiastic about ultimately moving into clinical trials with human patients to test the safety and tolerability of our boosting strategy and assess the actual efficacy of our vaccines, perhaps within a household context.”

The first inactivated influenza intranasal vaccine was administered in 2000. 

SELIN NALBANTOGLU
Selin Nalbantoglu covers breakthrough research for SciTech. She is a first-year in Saybrook College.