Vaccine adjuvants and their important immunological role.

Researchers have a better understanding of how some adjuvants work than others, says Darrell Irwin, an immunologist at the Massachusetts Institute of Technology in the US. Some of them are random, like Ramon’s discovery. For example, the mRNA vaccines made by Pfizer and Moderna use an ingredient called lipid nanoparticles that appear to act as adjuvants through pathways that are only partially understood. Some adjuvants are chosen more deliberately. On the other hand, in the Shingrix vaccine, scientists included as an adjuvant a molecule that is a component of certain types of infectious bacteria.

“Your immune system has evolved to recognize this molecule and creates a certain type of inflammation when it sees it,” Irwin says. “It kind of tricks your immune system into saying, ‘There’s something dangerous there. It looks like bacteria. And you have to trigger an immune response.”

Over time, adjuvants will be able to reprogram the genetic activity of immune cells to fight many diseases at once, not just those targeted by a particular vaccine, says Pulendran, who is working on the technique. Some research, including one from his laboratory, suggests this may be possible.

For example, in a combination of studies in mice and humans, the BCG vaccine against tuberculosis has been shown to protect against influenza, candida infections, staph infections, and respiratory infections.

Based on these studies, as well as data on the inflammatory molecules associated with these reactions, groups such as Pulendran’s are developing adjuvants, which he says aim to induce low levels of long-lasting antiviral immunity, like a lingering ember that simmers for weeks or months. and create greater resistance to all types of invaders. “It’s a kind of viral diagnostic inflammation that can be useful in fighting any infection,” he says; “They keep the fire of good inflammation burning at a tolerable level: not too bad, not too harmful.”

Work on adjuvants that precisely control inflammation opens up the possibility of developing vaccines that protect against diseases hitherto beyond vaccine reach, such as cancer, Irwin says. Ongoing trials of mRNA vaccines against melanoma and pancreatic cancer suggest that adjuvants (in this case lipid nanoparticles) combined with proteins produced by a person’s own tumors may help the body develop immunity against cancer. “We still don’t have truly effective therapeutic vaccines against cancer, but we might get there one day,” he says; “The latest data has people worried.”

At the heart of all these efforts to create more effective adjuvants and protect people from disease is the basic idea that to fight disease, our bodies need to produce just enough inflammation to fight the disease without causing too much disease. If our immune system can’t find balance on its own, perhaps we can develop solutions to do it for it.

Experts say the adjuvants of the future will likely evolve in parallel with the growing understanding of how inflammation works, and could help combat diseases that continue to plague humanity: HIV, malaria, cancer, new strains of influenza and SARS-CoV. 2 and any others that arise.

“A lot of vaccine research today is about thinking about how to create the right amount of inflammation and how to deliver it to the right place to help the immune response without making people feel like they’re infected with something,” he says. Irvine; “Advanced engineered adjuvants are likely to be an important part of finding ways to create vaccines for some really challenging scenarios.”