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The current mRNA vaccines from Moderna (Nasdaq:MRNA) and Pfizer (NYSE:PFE)/BioNTech (Nasdaq:BNTX) stimulate the production of neutralizing antibodies that bind to the spike protein of SARS-CoV-2.

But there is a novel mRNA vaccine that activates T cells to attack cells infected with the virus. Developed by researchers at MIT and other institutions, the new vaccine could sidestep the need for updated boosters based on currently circulating variants.

In a preclinical study published in Frontiers in Immunology, the T-cell vaccine successfully attacked cells infected with the virus rather than activating the part of the immune system that releases neutralizing antibodies. In addition, the researchers tested the vaccine in humanized mice and successfully generated both CD8+ (cytotoxic) and CD4+ (helper) T-cell responses.

This new MIT-T-COVID vaccine could ultimately be a new tool in protecting against severe illness or death across viral variants, but it won’t prevent transmission.

While the currently available mRNA vaccines don’t block transmission of SARS-CoV-2, they help slow its spread.

Variants continue to challenge immunity

While the current crop of COVID-19 vaccines has helped protect against severe illness and death, the emergence of multiple waves of SARS-CoV-2 variants has chipped away at their efficacy. As a result, vaccine developers have created bivalent vaccine boosters adapted to the BA.4/BA.5 sub-lineages of omicron.

The new, novel vaccine could potentially help fight flu and cancer in the future.

Scientists at MIT, Boston University, Tufts University, University of Texas and Acuitas Therapeutics collaborated on the research.

ML helped design the vaccine

In developing the vaccine, the researchers used machine learning (ML) algorithms to inform the selection of present or “conserved” peptides across viral variants. Peptides are molecules composed of short amino acid chains with peptide bonds. Out of thousands of options, the scientists identified about 30 to include in the vaccine.

The machine learning algorithms helped identify human leukocyte antigen (HLA) molecules with a high likelihood of alerting the immune system. “We used machine learning algorithms to predict which parts of the SARS-CoV-2 virus are going to activate the immune system in different individuals,” said Brandon Cater, a PhD student at MIT’s Computer Science and Artificial Intelligence Laboratory and lead author of the new paper.

“We were among the first to publish T-cell vaccine designs for COVID-19 that have broad population coverage, and the first to do a challenge study that demonstrated efficacy of these vaccines in a humanized mouse model using mRNA-LNP delivery,” Carter said. “Presently, others are going into clinical trials to test these approaches in humans, but there are not yet data on the efficacy.”

The researchers anticipate that a T-cell vaccine could help protect immunocompromised individuals who cannot produce adequate neutralizing antibodies. The new class of vaccines also has the potential to help people with long-COVID who continue to harbor reservoirs of SARS-CoV-2 long after their initial infection.

Paving the way to the future

According to Paul Offit, a director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, the findings could ultimately pave the way for developing the next generation of COVID-19 vaccines. “Given that T cells are critical in protection against severe COVID-19, future vaccines that focus on inducing the broadest T cell responses will be an important step forward in the next generation of vaccines,” he said in a news release.

In designing the T-cell vaccine, the researchers exercised caution to promote an immune response that was not overly strong. When the immune system goes into overdrive, it can trigger a process known as cytokine release syndrome, also known as a cytokine storm, which can cause lung damage.

T-cell vaccines attracting research

In November 2022, a separate group of researchers based at the University Hospital Tübingen in Germany published Phase 1 data indicating that another T-cell vaccine, CoVac-1, was well-tolerated and generated multifunctional CD4+ and CD8+ T-cell responses superior to from natural infections or other vaccine types. That research was published in Nature.

Whether adding a T-cell component to existing spike protein vaccines would drive more robust protection remains unclear. While eliciting T-cells and neutralizing antibodies could theoretically prompt a stronger immune response, MIT Professor David Gifford warned that the opposite is possible. That is, one part of the vaccine could interfere with the other.

In any event, answering that question will need to wait as studies will be required to establish the safety and efficacy of the T cell-eliciting vaccine.