Scientists Develop a Potential Universal Respiratory Vaccine

Stanford Medicine researchers have invented a new vaccine that protects mice from respiratory viruses, bacteria and allergens, which is the closest yet to a universal vaccine. The vaccine is delivered intranasally — such as through a nasal spray — and provides broad protection in the lungs for several months.

According to a news released published by the Stanford Medicine News Center, the new vaccine, known as GLA-3M-052-LS+OVA, mimics the T cell signals that directly stimulate innate immune cells in the lungs. It also contains a harmless antigen, an egg protein called ovalbumin or OVA, which recruits T cells into the lungs to maintain the innate response for weeks to months.

In the study, mice were given a drop of the vaccine in their noses, some of which recieved multiple doses, given a week apart. Each mouse was then exposed to one type of respiratory virus. With three doses of the vaccine, mice were protected against SARS-CoV-2 and other coronaviruses for at least three months. In addition, while these viruses often cause extreme weight loss in mice, the vaccinated mice lost much less weight and survived, and their lungs were nearly clear of the virus.

According to Bali Pulendran, PhD, the Violetta L. Horton Professor II and a professor of microbiology and immunology who is the study’s senior author, the prolonged innate response lowers the amount of virus in the lungs by 700-fold. And viruses that slip through this initial defense are met with a swift adaptive response in the lungs. “The lung immune system is so ready and so alert that it can launch the typical adaptive responses — virus-specific T cells and antibodies — in as little as three days, which is an extraordinarily short length of time,” Dr. Pulendran said. “Normally, in an unvaccinated mouse, it takes two weeks.”

The researchers then expanded their testing to bacterial respiratory infections, Staphylococcus aureus and Acinetobacter baumannii, and they found the vaccinated mice were protected against these, too, for about three months. In addition, they exposed the mice to a protein from house dust mites, a common trigger for allergic asthma. Allergic reactions are caused by a type of immune response known as Th2 response. Unvaccinated mice showed a strong Th2 response and mucus accumulation in their airways. The vaccine quelled the Th2 response, and vaccinated mice maintained clear airways.  

“I think what we have is a universal vaccine against diverse respiratory threats,” Dr. Pulendran said.

The next step is to test the vaccine in humans, first in a Phase I safety trial, then, if successful, in a larger trial in which vaccinated people are exposed to infections. Dr. Pulendran believes two doses of a nasal spray would be enough to provide protection in humans.

In the best case scenario, with enough funding, Pulendran estimates a universal respiratory vaccine might be available in five to seven years.