Scientists developing inhalable COVID-19 vaccine spray

New strategies would be easier to manufacture, do not require cold storage

In this rendition, a phage particle displays a region of the SARS-CoV-2 spike protein.

In this rendition, a phage particle displays a region of the SARS-CoV-2 spike protein.

Scientists at Rice University are part of an effort to develop an inhalable COVID-19 vaccine. The project, led by scientists at Rutgers University and Rice and Northeastern University, has produced two vaccine strategies. Both are scalable and adaptable and can be transported and stored at room temperature.

One strategy employs modified bacteriophage particles, also known as phage particles — viruses that infect and replicate in bacteria — that can be inhaled to deliver protection to the immune system via the lungs. The other delivers injectable, harmless adeno-associated virus phage particles that directly encode protection against the virus in immune cells. Both approaches triggered strong antibody production in rodents.

The U.S. National Science Foundation-funded study appears in Proceedings of the National Academy of Sciences. “This work is a great example of how simulations could help us understand biological processes and aid in the development of therapies,” said Wilson Francisco, a program director in NSF’s Division of Molecular and Cellular Biosciences.

Rice physicist Jose Onuchic, a co-principal investigator on the project, and his team worked on the first strategy. Scientists simulated several epitopes, the part of antigen molecules that binds to specific biological targets. These can be placed on the surface of bacteriophage particles, viruses that infect bacteria but are safe for humans and have been used to treat bacterial infections for almost a century.

The phage particles simulated at Rice and developed at Rutgers are engineered with an epitope — essentially, the part of a virus the immune system latches on to — from the SARS-CoV-2 spike protein, along with a small binding peptide that helps the phage cross from the lungs into the recipient’s bloodstream. Once there, they essentially teach the immune system to guard against COVID-19.

An advantage to a phage-enabled vaccine is that one spike protein can carry many epitopes, and they can be easily customized to protect against COVID-19 variants. “The protection derived from some of these epitopes may be destroyed in a variant, but the remaining ones will continue to offer protection,” Onuchic said.

The team’s initial task was to see which of a small set of epitopes displayed by SARS-CoV-2 would best serve the purpose. “We wanted to find fragments that mimic the spike structure, so they could be used to teach the immune system to recognize the virus,” said co-author Paul Whitford, a physicist at Northeastern University.

A single vaccine that protects against multiple COVID-19 variants and can be transported without the “cold chain” required for current vaccines will be key to curtailing the worldwide epidemic, according to Renata Pasqualini of Rutgers University, who co-led the study.

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