Cecilia Lee

A new Yale study will help develop a nasal COVID-19 vaccine that could make it easier to prevent infection and transmission of the virus. 

Researchers at the Yale School of Medicine, Benjamin Goldman-Israelow and Tianyang Mao GRD ’23, suggest that a different delivery of vaccination — a mucosal vaccine involving a nasal spray — could be better at preventing infection and transmission of the COVID-19 virus than the current vaccine shot to the arm. This study, guided by principal investigator and Professor of Immunobiology Akiko Iwasaki, is in preparation and will be shortly published as a preprint and submitted to a journal.

“The main reason we are developing a mucosal vaccine is because we have seen this unmet need that’s still current and very urgent,” Mao said. “COVID-19 cases are continuing to rapidly spread throughout the globe, and despite having an incredibly effective vaccine that can prevent the development of severe diseases and fatalities, we are still seeing SARS-CoV-2 transmission. This potentially hints at the potential ineffectiveness of the existing vaccines in preventing SARS-CoV-2 transmission.” 

The intramuscular vaccine injection has been the standard for the administration of immunizations throughout the pandemic. According to Mao, however, it has presented inherent incapability to induce long-lasting protective immunity at the mucosal surfaces, which is where Iwasaki’s team aims for the immune response to be. 

Mao added that there has been a lot of vaccine hesitancy, especially with COVID-19 vaccines, due to the nature of the vaccine being administered through an intramuscular injection to the arm.

“By inducing these immunological effector mechanisms including the mucosal antibody responses and tissue memory T-cell responses at the site of infection, we hope to induce faster immune responses,” Goldman-Israelow added. 

The hope, Goldman-Israelow said, is to potentially reduce transmission to others through quickly spotting and neutralizing the threat before it can get to deeper tissues in the nasal pathways and travel into the lungs. 

Two years ago, Goldman-Israelow and Mao found a fairly robust mucosal immune response in the lungs of mice infected with SARS-CoV-2. The findings were different from when mice were vaccinated intramuscularly, where lower levels of antibodies and other immune response effectors were discovered circulating in the lungs of mice. 

“We saw a pretty striking difference between infection and vaccination and wondered whether we could induce mucosal immunity using a vaccination strategy using mRNA vaccines,” Mao said. The Iwasaki team began to look at a mucosal vaccine that does not involve an arm injection and acts as nasal spray that is less invasive, creating a more localized immune response to quickly spot the threat.

Currently, nations around the world are worried about another global surge of the SARS-CoV-2 virus. The new Omicron variant has already been detected in at least 15 U.S. states; however, there is little information available on its behavior, its unique constellation of mutations and if existing vaccines are effective against it.

Omicron was first detected earlier this month. A majority of its 50 mutations are located on the SARS-CoV-2’s spike protein, which is the exposed part of the virus that binds with receptors on human cells. Scientists fear that this variant may have more transmissibility than the dominant Delta variant of concern. They are also concerned that it may be able to circumvent existing vaccines, or evade immune responses built up from past COVID-19 infection.

Scientists are scrambling to gather information on the latest strain designated to be a “variant of concern” by the Centers for Disease Control and Prevention. There is no evidence yet that existing COVID-19 vaccines, tests and treatments are any less effective against Omicron. Scientists will need to test the current COVID-19 vaccines or immune responses left behind by past infections against Omicron’s mutations.

Since this mucosal method is less invasive and creates a more localized immune response, the hope is to fight against the Omicron and future variants. In relation to variants, the researchers do not believe they are going to be inducing a major difference in the types of effectors that target and destroy the virus such as T-cells and antibodies. Rather, with this technology, the nasal spray can administer a locally higher concentration of those effectors at the sites of infection.

In addition, with mounting evidence that global vaccine equity can enable a path to normalcy, many Yale students hope that this mucosal vaccine shows promise. Omicron is a wake-up call about vaccine inequity and the need to deliver greater access, they said. 

“The idea of using mucosal vaccines that are delivered intranasally is extremely exciting because they have the potential to increase global access to COVID-19 vaccines,” Lydia Holtgrewe SPH ’23, who studies epidemiology focusing on microbial disease, wrote in an email. Current injectable formulations rely on the availability of hypodermic syringes and require cold-chains. Mucosal live attenuated influenza vaccines have been highly efficacious and easy to deliver in children in several African countries. The hope would be that a mucosal COVID-19 vaccine could ultimately decrease health inequities by offering a more affordable and feasible way to vaccinate people.

While the study faces challenges, there are promising advances to address them and it highlights recent progress in the development of vaccines against COVID-19 and future communicable diseases. 
There were 50 new and probable cases of the Omicron variant on Dec. 6.

Natalie Makableh covers the intersection of health, scientific research and technology at Yale. Originally from San Francisco, California, she is a graduate student at YaleEMD specializing in emerging infectious diseases.