South SFV Today

Researchers at Stanford Engineering have developed a nanoparticle platform that could enhance the effectiveness of existing vaccines, including those for influenza, COVID-19, and HIV. The platform aims to help vaccine candidates produce stronger and longer-lasting immune responses while allowing researchers to test different types of immune responses to determine their efficacy against specific pathogens.

“These nanoparticles elicit stronger, more robust immune responses, and the breadth of our platform allows us to readily tune the type of immune response in a way that just was not feasible with previous technologies,” said Eric Appel, an associate professor of materials science and engineering and senior author on the paper published Aug. 7 in Science Advances. “This can be a tool to understand how different types of immune responses give rise to better or worse protection – it was impossible to even ask that question before.”

Modern vaccines typically teach the immune system to recognize and fight infections by introducing fragments of pathogens. However, these fragments may not provoke strong reactions alone; hence, adjuvants are used to stimulate the body’s immune response. Currently available adjuvants are limited in number and vary widely in effectiveness.

“We wanted to create as potent an adjuvant as possible,” said Ben Ou, a doctoral student in Appel’s lab and first author on the paper. “We combined two different adjuvant technologies to create a nanoparticle platform that will activate different immune pathways and improve vaccine responses.”

The team attached toll-like receptor agonists (TLR agonists) molecules—which interact with receptors on innate immune cells—to a base nanoparticle made from saponin molecules. Saponins have been effective adjuvants for decades, including use in the Novavax COVID-19 vaccine. This combination produced an adjuvant that acted through multiple immune pathways resulting in broad, strong, long-lasting responses.

Ou, Appel, and colleagues tested their TLRa-SNP adjuvants with both COVID-19 and HIV vaccine candidates. The results showed significantly improved effectiveness compared to versions paired with existing adjuvants; they were more potent and lasted longer while also creating immune responses capable of detecting multiple pathogen variants.

The researchers created five versions of their adjuvants using various TLR agonists attached to the saponin nanoparticle base. Each version generated slightly different types of immune responses by activating distinct signaling proteins.

“All our adjuvants improve overall vaccine responses but the specific types of improvements are different,” Ou stated. “If we know that a specific type of immune activation will confer better protection, we now have a platform that will allow you to pick the specific formulation that will drive that distinct response.”

With current adjuvants being too varied for detailed studies into which type provides optimal protection against particular pathogens, this new interchangeable TLR agonist-based platform offers enhanced flexibility for tailoring specific immunological outcomes while maintaining robust activation levels.

Other TLR agonists beyond those tested could be paired with this platform according to Ou who is keen on further investigations involving multiple types simultaneously—an already proven possibility aimed at crafting bespoke nanoparticle adjuvants tailored towards maximum efficacy.

“This platform approach will open up opportunities for people in the field asking more probing questions about what immunology works better under varying contexts," Appel added "And it’s also making significantly better adjuvants."

Appel holds affiliations across several Stanford institutes including Bio-X; Cardiovascular Institute; Wu Tsai Human Performance Alliance; Maternal & Child Health Research Institute; Cancer Institute; Neurosciences Institute alongside Sarafan ChEM-H as faculty fellow among others involved notably Bali Pulendran from School Medicine alongside postdoctoral researcher Julie Baillet plus numerous graduate students among co-authors listed within research effort spanning University Washington collaboration funded via entities such Bill Melinda Gates Foundation along National Institutes health agencies inclusive Eastman Kodak Fellowship & NSF grants etcetera ensuring wide-ranging backing underpinning this innovative scientific venture spotlighted herein.

Media contact:

Jill Wu

School Engineering: jillwu@stanford.edu

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