Protein Discovery Sparks Hope for Extended COVID Defense

La Trobe University

A protein particle hidden within the SARS-CoV-2 virus could lead to longer-lasting, more protective vaccines for COVID-19.

Scientists from La Trobe University and Kumamoto University in Japan have discovered that the body's immune system strongly reacts to an internal protein from SARS-CoV-2, the virus that causes COVID-19, which mutates less frequently than the surface-spike protein currently targeted by vaccines.

New research published in 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.

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

"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," Professor 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."

Professor Gras said the development of a longer-lasting vaccine could mean that people would need fewer booster vaccines to fight COVID, and help protect against the development of Long COVID.

"The more people get vaccinated, the more we're protecting the population, which helps to reduce the virus's death toll and the impact of the infection itself," Professor Gras said.

"But there is more than just COVID – we now know that about 10 per cent of the population is impacted by Long COVID and the more you catch the virus, the more likely you can develop Long COVID."

Professor Gras, Dr Demetra Chatzileontiadou, Dr Janesha Maddumage, and PhD candidate You Min Ahn led the research team at LIMS and La Trobe University's School of Biomedicine, Agriculture and Environment (SABE).

It was funded through Professor Gras's National Health and Medical Research Centre (NHMRC) Leadership Investigator Grant (L2) and her Medical Research Future Fund (MRFF) grant to investigate COVID.

The research was done in collaboration with Associate Professor Chihiro Motozono and Yoshihiko Goto from the Joint Research Center for Human Retrovirus Infection at Kumamoto University in Japan, with data collection by the Australian Synchrotron.

Professor Gras will also lead a new research centre at La Trobe University which aims to uncover the cause of Long COVID and other life-limiting post-viral infections such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis (MS).

The Post-Acute Viral Infection diseases Group (PAVING) Centre of Research Excellence has received $3 million in Federal funding from the National Health and Medical Research Council (NHMRC).

La Trobe University will host Long COVID 2025 on 12 September. The conference aims to foster collaboration nationwide and drive innovation in research, healthcare and policy.

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