Vaccines of the future: Harnessing the immune system for long-lasting protection

The WEHI-led study used a novel approach combined with cutting-edge mRNA vaccine technology to increase the formation of a type of T cell which has remarkable self-renewing capacity and can remember threats for years and even decades.

The mouse-based study, published in the Journal of Experimental Medicine, uncovered a new way to enhance stem cell-like memory CD8+ T cells following vaccination, pointing to a future where more diseases are vaccine-preventable and treatable, and where regular vaccine boosting is no longer needed.

At a glance

• WEHI researchers have developed a novel mRNA vaccine strategy to boost the production of a type of T cell which is critical for long-lasting immune memory.

• These stem cell-like memory CD8+ T cells are key for clearing infections, driving the elimination of cancerous cells, and can provide decades-long protection.

• The study brings more effective, longer-lasting vaccines against viruses, and even cancer, closer.

Super vaccines

Vaccines are the most effective preventative medicine in history and continue to save millions of lives every year.

Despite their outstanding success, vaccines often rely on antibodies for immune protection. These naturally fade over time, necessitating the need for boosters to ensure enhanced immunity -- like we receive to protect against COVID-19 and tetanus.

Antibodies target the surface of a virus or cancerous cell. When these change, as is the case of rapidly mutating viruses like influenza and COVID-19, we need regular boosters that target new circulating variants.

Lead author on the study, WEHI Immunology division head Associate Professor Joanna Groom, said a specific type of immune cell had shown exceptional promise at overcoming these two obstacles.

"We've believed for some time that stem cell-like memory CD8+ T cells correlate with long-lasting protection, and this study is the first to prove this benefit," said Assoc Prof Groom.

Like elephants, stem cell-like CD8+ T cells have the ability to 'remember' previous infections and respond rapidly to threats.

The team harnessed immunomodulation, to adjust immune responses at the cellular level, alongside mRNA vaccine technology to promote the generation of these potent cells in mice.

mRNA vaccines, like those used to protect against COVID-19, are highly adaptable and can be quickly generated to tackle new and emerging viral threats, making them a highly promising tool for vaccine development.

"The results are really striking -- we were incredibly excited at how effective our new vaccine strategy was at boosting these cells," Assoc Prof Groom said.

"Our approach has the potential to reduce the need for frequent booster shots, while maintaining strong and lasting immunity.

"Inducing these stem cell-like memory CD8+ T cells is the next big challenge for improving vaccines, and we're energised to bring this future closer."

Cancer vaccine potential

In addition to viruses, increased numbers of these cells are associated with improved cancer outcomes.

Study first author, PhD student Benjamin Broomfield, said this indicated that the findings could inform new cancer immunotherapies.

"We know the body needs these cells to eliminate cancerous cells and our lab is now focused on applying the approach used in this study to boost stem cell-like CD8+ T cells to tackle cancer," said Broomfield.

"A therapeutic vaccine for cancer would be a total game-changer, and we're optimistic about where this research can go."