Workflow for the generation of SARS-CoV-2-derived HLA I and HLA II immunopeptidome data. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-51959-6

Melbourne researchers have discovered more than 200 new vaccine target candidates from the COVID-19 virus, SARS-CoV-2, that could lead to the development of vaccines with a longer lasting broader immunity than existing vaccinations.

In a paper published in the journal Nature Communications, research led by Prof Anthony W. Purcell and first-authored by Dr. Asolina Braun from the Monash Biomedicine Discovery Institute, investigates seven proteins of the COVID-19 virus that could become targets for new vaccines.

The initial vaccines designed to combat COVID-19 were targeted against the original Wuhan strain Spike protein. However, while this approach led to the generation of several highly effective, safe vaccines within an astonishingly brief timeframe, it also comes with some limitations, according to Dr. Braun. “The SARS-CoV-2 virus has mutated its Spike protein leading to lower efficacy of current vaccines,” she said.

“Also, the original vaccines focused on B cell-mediated antibody responses for developing immunity. We now know that recruiting the other arm of the immune system, the T cells, can help to maintain immunity for longer.”

In the study the researchers describe more than 200 SARS-CoV-2-derived peptides that could be targets for new and improved vaccines against COVID-19 and validate that a number of those peptides can trigger T cell responses in convalescent individuals.

Reflecting on this achievement, lead investigator Prof Tony Purcell remarks, “As part of a long term collaboration with Evaxion Biotech, we pivoted and turned our attention to SARS-CoV-2 during the pandemic. Rather than continue the mainstream attention that focused predominantly on the Spike glycoprotein, we turned our attention to other more conserved viral proteins as potential next generation vaccine targets.

“The combination of the Monash team’s epitope discovery by immunopeptidomics and protein chemistry, T cell immunology at the Peter Doherty Institute and Evaxion’s AI-guided bioinformatics expertise was critical to the development of this paper that highlights the potential of several conserved viral proteins as vaccine candidates.”

According to Dr. Braun, COVID-19 still continues to pose a high burden on health systems worldwide, and “this continued burden is mainly caused by the spread of several new variants. Thus, an unmet need remains for the development of novel vaccines able to target several viral strains and confer wide-spread protection in the global population,” she said.

“The next generation of vaccines will benefit from eliciting both B-cell and T-cell mediated immunity toward multiple COVID proteins. Our study has uncovered promising candidates for the development of just such vaccines.”