Researchers at the La Jolla Institute for Immunology have helped develop a computational approach that could make future vaccines more effective across people with different genetic backgrounds.
Working with Ben-Gurion University of the Negev in Israel, the La Jolla team developed a system to identify rare protein fragments that can interact with multiple versions of key immune-system molecules known as HLAs. The work was published in the Proceedings of the National Academy of Sciences.
“This is fantastic and exciting work,” said Alessandro Sette of the La Jolla Institute for Immunology, a co-author of the study. “We have known for some time that peptides that bound many different HLAs were prominent in responses to microbes and allergens, but a strategy to synthetically identify these sequences was lacking.
“This study takes the issue of ‘super epitopes’ to a new level and promises to facilitate our characterization of immune responses, and also the design of powerful immunogens.”
HLAs are among the most variable components of the human immune system, with more than 22,000 known variants. Because each person carries a different combination, immune responses to the same vaccine can vary widely, and some immune-triggering fragments may go unrecognized in certain individuals.
To address that challenge, the researchers built a computational framework called “Super HLA” that scans large numbers of candidate peptides and predicts which are most likely to bind across multiple HLA types. The system uses probabilistic modeling and machine-learning tools and removes sequences that resemble human proteins.
The model screened more than 190,000 candidate peptides and narrowed them to 100 for laboratory testing at the La Jolla Institute.
Of those, 24 were confirmed as “superbinders,” meaning they could bind across multiple HLA groups. Twenty-one bound to at least four HLA supertypes, and one bound to nine of the 12 tested in the study.
Professor Tomer Hertz of Ben-Gurion University, which is collaborating with the La Jolla Institute of Immunology. (Photo by Liel Cohen-Lavi)Only a small number of similarly broad-binding peptides have previously been documented inimmunology databases, suggesting they may have been overlooked rather than being truly rare. The findings also suggest these peptides can be identified systematically rather than discovered by chance, potentially reshaping how scientists search for vaccine targets.
Researchers said the approach could be applied to vaccine development for infectious diseases, cancer immunotherapy and pandemic preparedness, and may improve immune coverage in populations that have historically been underrepresented in immunology data.
The study was led by Tomer Hertz of Ben-Gurion University’s Faculty of Health Sciences, along with graduate students Elinor Peer and Liel Cohen-Lavi, in collaboration with scientists at the La Jolla Institute.
Hertz said the project traces back roughly 15 years to conversations with a colleague while both were postdoctoral researchers at the Fred Hutchinson Cancer Center in Seattle.
“Good ideas are worth continuing to dig into, even long after the first sketch was drawn on the whiteboard,” Hertz said.
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