Combining Forces
In the new study, researchers tested five different combinations of TLR agonists hooked to the saponin nanoparticle framework. Each elicited a slightly different response from the immune cells.
“Our immune systems generate different downstream immune responses based on which TLRs are activated,” Dr. Ou said.
Ultimately, the advance could spur the development of vaccines tuned for stronger immune protection.
“We need different immune responses to fight different types of pathogens,” Dr. Ou said. “Depending on what specific virus/disease the vaccine is formulated for, activation of one specific TLR may confer better protection than another TLR.”
According to Dr. Burkhart, combining a saponin with a TLR agonist has found success before.
Biopharma company GSK (formerly GlaxoSmithKline) used the combination in its AS01 adjuvant, in the vaccine Shingrix against herpes zoster. The live-attenuated yellow fever vaccine, given to more than 600 million people around the world and considered one of the most powerful vaccines ever developed, uses several TLR agonists.
The Stanford paper, Dr. Burkhart said, “is a nice demonstration of the enhanced efficacy [that] adjuvants can provide to vaccines by exploiting the synergy different adjuvants and TLR agonists can provide when used in combination.”
Tailoring Vaccines
The customizable aspect of TLR agonists is important too, Dr. Burkhart said.
“The human immune system changes dramatically from birth to childhood into adulthood into older maturity,” he said. “It’s not a one-size-fits-all. Vaccines need to be tailored to these populations for maximum effectiveness and safety. TLRAs [TLR agonists] are a highly valuable tool in the vaccine toolbox. I think it’s inevitable we’ll have more in the future.”
That’s what the Stanford researchers hope for.
They noted in the study that the nanoparticle platform could easily be used to test different TLR agonist adjuvant combinations in vaccines.
But human studies are still a ways off. Tests in larger animals would likely come next, Dr. Ou said.
“We now have a single nanoparticle adjuvant platform with formulations containing different TLRs,” Dr. Ou said. “Scientists can pick which specific formulation is the most suitable for their needs.”
A version of this article first appeared on Medscape.com.