Researchers at Stanford Engineering have developed a new nanoparticle platform that could significantly improve the effectiveness of existing vaccines, including those for influenza, COVID-19, and HIV.
This innovative platform not only helps vaccines produce stronger and longer-lasting immune responses but also allows scientists to explore different types of immune responses to determine which are most effective in protecting against specific pathogens.
The breakthrough, led by Eric Appel, an associate professor of materials science and engineering, was detailed in a paper published in Science Advances on August 7.
The study describes how these nanoparticles can be tailored to elicit specific immune responses, a capability that was previously unattainable with older technologies.
A New Type of Adjuvant
Modern vaccines typically work by introducing a fragment of a pathogen—such as a protein from the coronavirus—into the body to train the immune system to recognize and fight the real virus.
However, these fragments alone may not trigger a strong enough immune response, which is why vaccines often include adjuvants. Adjuvants are substances that enhance the body’s immune response to the vaccine.
Unfortunately, there are only a few adjuvants currently approved for clinical use, and their effectiveness can vary greatly.
To address this, the Stanford team set out to create a more potent adjuvant. They combined two different adjuvant technologies to develop a nanoparticle platform that activates multiple immune pathways, thereby improving vaccine responses.
The key innovation involved attaching molecules known as toll-like receptor agonists (TLR agonists) to a base nanoparticle made of saponin molecules. Saponins have been effective adjuvants for years, including in the Novavax COVID-19 vaccine.
The resulting adjuvant, called TLRa-SNP, worked through several immune pathways, leading to a broad, strong, and long-lasting immune response.
When tested with COVID-19 and HIV vaccine candidates, the TLRa-SNP adjuvants greatly enhanced the vaccines’ effectiveness, making them more potent and longer-lasting compared to versions using existing adjuvants.
Remarkably, the COVID-19 vaccine candidate paired with TLRa-SNP was effective against multiple variants of the virus, including delta and omicron.
Customizing Immune Responses
The platform’s flexibility is one of its most significant advantages. There are multiple types of TLR agonists, each binding to different immune receptors.
By swapping out these TLR agonists on the saponin nanoparticle base, the researchers created five different versions of their adjuvants, each producing a slightly different immune response. This allows for a more tailored approach to vaccine development.
“All of our adjuvants improve overall vaccine responses, but the specific types of improvements are different,” explained Ben Ou, a doctoral student in Appel’s lab and the study’s first author.
“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.”
This flexibility sets the TLRa-SNP adjuvants apart from existing adjuvants, which are too different from each other to allow for precise investigations into which type of immune response is most effective against a given pathogen.
The new platform enables researchers to tweak the immune response while maintaining strong activation, offering a powerful tool for vaccine development.
The researchers are also exploring other TLR agonists that could be paired with this platform, and they are investigating the potential of using multiple TLR agonists simultaneously to create even more effective adjuvants.
The goal is to develop bespoke nanoparticle adjuvants tailored to provide the most robust protection against a wide range of diseases.
“This platform approach will open up opportunities for people in the field to ask more probing questions about what immunology works better in different contexts,” Appel said. “And it’s also making significantly better adjuvants.”
The new nanoparticle platform represents a significant advance in vaccine technology, offering the potential to create vaccines that are not only more effective but also more adaptable to the challenges posed by evolving pathogens.
As research continues, this technology could play a crucial role in the fight against current and future diseases.
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The research findings can be found in Science Advances.
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