A new bacterial delivery system aims to administer a COVID-19 vaccine directly to the respiratory tract as a nasal spray, prompting an immune response directly at the site where the SARS-CoV-2 virus likely invades and multiplies.

Based on the approach of a team of virologists at the University of Nebraska–Lincoln (Lincoln, NE, USA), bioengineered Lactobacillus - a safe, widely used bacteria best recognized for its role in fermenting yogurt and cheese - would deliver antigens, the vaccine component that triggers an immune response, directly to the mucosal tissues of the nose and mouth. This site-specific strategy may provide more robust protection against COVID-19 than an injected vaccine because it would more closely mimic a natural COVID-19 infection, producing antibodies and immune cells in the key locations where the virus enters.

With a spray vaccine, the team aim to capitalize on some of the uniquely powerful components of the body’s immune machinery that are located in mucosal tissues. The B cells there produce immunoglobulin A, or IgA, which is the body’s powerful first-line defense against pathogens in the gut and airway. Mucosal tissues are also rich in memory T cells, which are able to “remember” specific antigens after crossing paths with them the first time, enabling them to produce a faster, stronger immune response at the next encounter.

Lactobacillus as a vaccine vector offers several advantages. For one, as a food-based platform, it is unquestionably safe. People routinely consume Lactobacillus in yogurt and other probiotic supplements. It is also able to colonize the mucosal tracts, meaning it lives and multiplies in harmony with the airway’s other bacteria. The virologists hope that this means its protective effects will last longer, minimizing the number of times an individual needs the vaccination. Lactobacillus is also relatively inexpensive to produce and amenable to genetic modification, meaning that the virologists can genetically engineer the bacteria to produce SARS-CoV-2 antigens. This allows them to skip the costly and difficult process of antigen purification, which is required for traditional protein-based vaccines.

There are other economic benefits to a nasal spray vaccine. It will not require needles, cutting equipment costs. And it will not necessarily require trained health care workers as people may be able to administer the nose spray themselves. These characteristics make nasal spray vaccines a potentially viable solution for developing countries, which are struggling to secure doses of the leading COVID-19 vaccine candidates. Accordingly, the virologists are also in the early phases of exploring a Lactobacillus-based COVID-19 vaccine. With support from the Office of Research and Economic Development’s COVID-19 Rapid Response Grant Program, the virologists are using a pseudotyped COVID-19 virus to evaluate the effectiveness of the antibodies induced by the engineered bacteria. They are confident that their work will be valuable in the fight against COVID-19 and future viruses that jump from wildlife to humans.

“Mucosal vaccination should be effective because mucosal vaccines induce immunity at the point of viral entry, controlling early infection before it becomes an established systemic infection,” said Shi-Hua Xiang, associate professor of veterinary medicine and biomedical sciences and a member of the Nebraska Center for Virology. “The long-term goal is to make an effective mucosal vaccine for respiratory-transmitted viral infections diseases.”

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