Studies provide hope for more protective COVID vaccines

A protein particle hidden within the SARS-CoV-2 virus could lead to longer-lasting, more protective vaccines for COVID-19, according to scientists from La Trobe University and Kumamoto University.

The scientists discovered that the body’s immune system strongly reacts to an internal protein from SARS-CoV-2, which mutates less frequently than the surface-spike protein currently targeted by vaccines. Research published in the journal Nature Communications shows that these protein particles, known as peptides, appear on the surface of infected cells via an immune molecule called HLA-C, which killer T cells then use to identify and eliminate infection.

Lead researcher Distinguished Professor Stephanie Gras, Deputy Director of the La Trobe Institute for Molecular Science, said the discovery could open the way for the development of new vaccines and treatments that offered protection across multiple strains of SARS-CoV-2.

“Currently, vaccines target the spike proteins that decorate the surface of the virus — but they mutate frequently as they are constantly under pressure by our immune cells, which means we might need a new vaccine for each new variant,” Gras said.

“We found that the killer T cells, which also fight infection, can be activated by a protein that forms a part of the shell that protects the virus’s genetic material, like the yolk of an egg.

“Because this protein is inside the virus, it mutates much less frequently — knowledge which could guide the development of vaccines and therapeutics that are still effective as the virus evolves,” Gras added. She said the creation of a longer-lasting vaccine could mean that people would need fewer booster vaccines to fight COVID and decrease their risk of developing long COVID, as the more you catch the virus, the more likely you can develop long COVID.

Meanwhile, a separate study led by the Centenary Institute and The University of Sydney shows that a new nasal vaccine could offer powerful protection against COVID-19, by stopping infection in the nose before the virus spreads through the body.

Published in Frontiers in Immunology, the study tested a nasal vaccine made from the SARS-COV-2 spike protein combined with Pam2Cys, an immune-boosting compound developed at The University of Sydney. Unlike current injected vaccines, which are highly effective at preventing severe illness but less effective at blocking infection and transmission, the nasal vaccine builds immune defences directly in the upper airways where the virus first takes hold.

In preclinical models involving mice, the nasal vaccine triggered strong immune defences in both the nose and bloodstream. When used after a standard COVD-19 injection, it acted as a powerful booster and provided full protection, with no virus detected in the lungs and brain.

“Our study shows that a nasal vaccine can build strong immune defences right where the virus first enters the body — the nose — to help prevent infection,” said senior co-author Professor Warwick Britton, from the Centenary Institute’s Centre for Infection & Immunity.

“Used as a booster after a standard injection, it also gave protection to vital organs like the lungs and brain. These results highlight the advantages of targeting immunity in the upper airways.”

Senior study co-author Dr Anneliese Ashhurst, from The University of Sydney, added, “Nasal vaccines could work hand in hand with current COVID-19 vaccines. By blocking the virus in the nose before it spreads, we not only reduce the risk of severe illness but also potentially cut transmission in the community. That’s essential for lowering overall case numbers and limiting the rise of new variants.”

First author Dr Erica Stewart, who was a researcher at the Centenary Institute when the work was undertaken, said the findings strongly support further development of Pam2Cys-based vaccines.

“Pam2Cys has shown it can boost immune responses in the nose, where protection is most needed,” she said. “Our findings highlight its promise as a powerful new approach to strengthening protection against COVID-19.”

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