Researchers at the University of Wisconsin School of Veterinary Medicine announced on Mar. 31 that they have identified a possible way to create longer-lasting vaccines for respiratory viruses such as influenza and the coronavirus that causes COVID-19.
This research, published in Cell Reports on March 25, focuses on T cells, which are immune cells that help control infections by killing virus-infected cells. Unlike antibodies, which are the basis of most current vaccines and can lose effectiveness as viruses mutate, T cells recognize more stable parts of viruses. This could provide broader protection.
M. Suresh, professor in the Department of Pathobiological Sciences who led the study, said: "We have discovered essentially a mechanism which we can target - a new clue to generating long-lived T cells." Suresh explained that while most vaccines stimulate antibodies to block infection—a method effective for many diseases—this approach can be less effective against rapidly evolving viruses like SARS-CoV-2 and seasonal influenza.
Suresh said: "So, what do we do? We need a plan B." Currently, this has meant updating vaccines regularly and encouraging annual shots. However, vaccination rates have been declining in recent years. "With the pandemic we went through, people are just tired of getting vaccinated," Suresh said.
Harnessing T cells may offer an alternative by limiting disease severity rather than preventing infection outright. "They go and hunt one infected cell at a time and eliminate them," Suresh said. The challenge has been making these protective effects last longer—especially in tissue-resident memory T cells found in the lungs.
Suresh's team studied how early inflammatory signals after vaccination affect memory T cell development using an experimental vaccine approach in mice. They compared viral-like inflammation with bacterial-like inflammation and found notable differences: "When we had a virus-like inflammation, the memory T cells dropped off and we quickly lost protection," Suresh said. "But when we created a bacterial-like inflammation, the mice developed a different kind of memory T cell which actually persisted longer and protected longer." These long-lasting cells also showed flexibility when exposed to infection: "They just flipped," Suresh said.
The findings suggest it may be possible to design vaccines requiring fewer boosters while offering broad protection across variants. As Suresh put it: "The duration of immunity is really, really important... Can we vaccinate fewer times, and can shots protect against new strains?"
Future research will test this approach in nonhuman primates and explore methods to direct immune responses specifically to lung tissue after traditional vaccination.
