Nasal COVID-19 vaccine blocks infection, animal studies show

A new study by researchers at Washington University School of Medicine in St. Louis shows that next-generation vaccines that target the virus's entry points, the nose and mouth, may be able to limit the spread of respiratory infections and prevent infections that traditional injections cannot. Using an intranasal COVID-19 vaccine based on Washington University technology approved for use in India and licensed to Ocugen Inc. for further development in the United States, the researchers demonstrated that infected vaccinated hamsters did not transmit the virus to other hamsters, breaking the cycle of infection. In contrast, approved COVID-19 vaccines administered by injection failed to prevent the spread of the virus.

The survey results, released on July 31, Scientific advancesprovides further evidence that so-called mucosal vaccines, which are sprayed into the nose or dropped into the mouth, could be key to controlling respiratory infections such as influenza and COVID-19 that still spread and cause serious illness and death.

“To prevent infection, we need to keep the viral load low in the upper respiratory tract,” said Dr. Jacko Boone, professor of medicine, molecular microbiology, and pathology and immunology, and senior author of the paper. “The less virus there is in the first place, the less likely you are to infect someone else by coughing, sneezing, or even just breathing. This study shows that a mucosal vaccine is better than an injected vaccine at limiting viral replication in the upper respiratory tract and preventing transmission to the next person. We will need such a vaccine in an epidemic or pandemic situation.”

Developing a vaccine that can control virus levels in the nasal cavity has proven difficult. Viruses such as influenza virus, SARS-CoV-2 (the virus that causes COVID-19), and respiratory syncytial virus (RSV) multiply rapidly in the nasal cavity and spread from person to person within a few days of initial exposure. Traditional injected vaccines can take up to a week to generate a maximal immune response and are much less effective in the nasal cavity than in the bloodstream, leaving the nasal cavity relatively vulnerable to fast-growing and fast-spreading viruses.

In principle, a vaccine sprayed or dropped directly into the nose or mouth could reduce infection by limiting viral replication and eliciting an immune response where it is needed most. However, evidence that mucosal vaccines actually reduce infection has proven difficult to gather. Animal models of infection are not well established, and tracking person-to-person transmission is extremely complicated given the number and types of contacts the average person experiences every day.

For this study, Boone and colleagues developed and validated a community-transmission model in hamsters, which they then used to evaluate the effect of mucosal vaccination on the spread of SARS-CoV-2. (Unlike mice, hamsters are susceptible to infection with SARS-CoV-2, making them an ideal laboratory animal for studying transmission.)

The researchers immunized groups of hamsters with laboratory versions of approved COVID-19 vaccines, such as the nasal iNCOVACC used in India or the injectable Pfizer vaccine. For comparison, some hamsters were not immunized. After waiting a few weeks for the immune response of the vaccinated hamsters to fully mature, the researchers infected other hamsters with SARS-CoV-2 and placed the immunized hamsters with the infected ones for eight hours. This first phase of the experiment mimicked the experience a vaccinated person would have if exposed to a COVID-19 patient.

After eight hours of contact with the infected hamsters, most of the vaccinated animals became infected. Virus was found in the nose and lungs of 12 of 14 hamsters (86%) that received the intranasal vaccine and 15 of 16 hamsters (94%) that received the injected vaccine. Importantly, although most animals in both groups were infected, the extent of infection was not the same. Virus levels in the respiratory tract of nasally immunized hamsters were 100-100,000 times lower than in injected and unvaccinated hamsters. The health of the animals was not evaluated in this study, but previous studies have shown that both vaccines reduce the chance of severe illness and death from COVID-19.

The second phase of the experiment produced even more surprising results: The researchers then placed the vaccinated hamsters, which then developed an infection, together with healthy vaccinated and unvaccinated hamsters for eight hours, to model the transmission of the virus from a vaccinated person to another.

Hamsters that came into contact with hamsters vaccinated via the nose did not become infected, regardless of whether the vaccinated hamster had been vaccinated or not. In contrast, about half of the hamsters that came into contact with hamsters vaccinated via injection became infected, again regardless of the immune status of the vaccinated hamster. In other words, nasal vaccination, but not via injection, broke the cycle of infection.

Boone said these data could be important as the world prepares for the possibility that avian influenza currently circulating among dairy cows could jump to humans and cause an influenza pandemic. An injectable avian influenza vaccine already exists, and a research team at the University of Washington is working to develop an intranasal avian influenza vaccine. The team includes Boone and Michael S. Diamond, M.D., Ph.D., the Herbert S. Gasser Professor of Medicine and one of the inventors of the intranasal vaccine technology used in the paper.

“Mucosal vaccines are the future of respiratory infection vaccines,” Boone said. “Historically, developing such vaccines has been challenging. There's a lot we still don't know about the type of immune response that's needed and how to elicit it. I think we'll see a lot of very exciting research in the next few years that will lead to major improvements in respiratory infection vaccines.”