They said that the current COVID-19 vaccines, designed to trigger an antibody response to the SARS-CoV-2 spike protein, were vulnerable to mutations that could make the vaccine less effective over time.
They partnered with Evaxion Biotech, a biotechnology firm based in Denmark, on the study, which is published in the journal Frontiers in Immunology.
Upon being challenged with a lethal dose of SARS-CoV-2, the researchers found that 87.5 per cent of the mice vaccinated with the T-cell-based vaccine survived while only one of the control-group mice survived.
All the vaccinated mice that survived were also found to have cleared the infection within 14 days post-challenge.
“To our knowledge, this study is the first to show in vivo [in a living organism] protection against severe COVID-19 by an AI-designed T-cell vaccine,” said Girish Kirimanjeswara, associate professor of veterinary and biomedical sciences, Penn State.
“Our vaccine was extremely effective at preventing severe COVID-19 in mice, and it can be easily scaled up to start testing it in humans, as well,” said Kirimanjeswara. According to Kirimanjeswara, the spike protein of the SARS-CoV-2 virus is under heavy selection pressure, which can result in mutations that drive the emergence of new variants.
“This means that [mRNA] vaccine manufacturers will have to keep creating new vaccines that target new variants, and people have to keep getting these new vaccines,” he said.
Instead of targeting the constantly mutating spike protein, the team at Evaxion Biotech designed a vaccine that included 17 epitopes, or sites on antigen molecule, from various proteins of SARS-CoV-2 that are recognized by the immune system.
The researchers said that these epitopes elicit an immune response from a broad selection of T cells, ensuring a sustained coverage of future variants.
One advantage of this, Kirimanjeswara said, was that the virus would have to undergo too many mutations to be able to escape this T-cell-mediated immunity. The other one, he said, was that repeated booster doses would not be needed owing to the immunity conferred by T-cells, which is usually long-lasting.
He said that it was harder and more time-consuming to produce a T-cell-based vaccine than an antibody-based one.
“Given the urgency with which we needed a vaccine to address the COVID-19 pandemic, it makes sense that vaccine manufacturers created an antibody-based vaccine. Now that the urgency has passed, a second-generation T-cell-based vaccine could be more effective and last longer,” he said.
The study’s co-author Anders Bundgaard Sorensen, project director, Evaxion Biotech, said that this vaccine used multiple types of artificial intelligence in a platform called RAVEN (Rapidly Adaptive Viral rEspoNse) to predict ideal targets for vaccines.
“RAVEN is really adaptable,” Sorensen said. “We don’t have to wait for a new strain of a virus to arrive to develop a vaccine. Instead, we can predict what will be needed in advance.”
Sorensen noted, “It’s much easier to get broad coverage with a T-cell vaccine, as we can include multiple epitopes targeting different proteins.”
Sorensen said that because RAVEN could predict what was needed, it could also be used to develop better influenza vaccines, in addition to producing better COVID-19 vaccines.