Watertown Journal Club - Improving Vaccine Immunogenicity with Corner Therapeutics
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Watertown Bio Journal Club is a monthly publication highlighting the scientific research produced by labs in Watertown. If you’re a Watertown-based biotech and have a recently published article, pre-print, or conference publication you would like featured in our next issue, reach out at newsletter@watertown.bio. If you enjoy our publications consider supporting us.
Featured Article: An NLRP3-stimulatory adjuvant improves the immunogenicity of influenza virus vaccines in mice and non-human primates
As Corner Therapeutics transitions from the Arsenal on the Charles to 99 Coolidge Ave, we thought it would be worthwhile to highlight their recent publication in mBio. Corner’s programs focus on modulating dendritic cells to enhance immune system function, either to generate T-cell therapies to fight cancer or to improve the immune response to a vaccine, which is the focus of this article.
In this work, scientists at Corner describe a novel adjuvant, which is a molecule that activates the innate immune system to help trigger an immune response to the vaccine’s antigen. Their goal was to address variability in immune response to vaccines due to inconsistent activation of dendritic cells (which are responsible for activating the T-cells and B-cells that mediate adaptive immunity) by designing an adjuvant that would maximally activate (which they term “hyperactivation”) these cells. They engineered a combination TLR7/8 receptor agonist that when paired with a novel lipid CT009 induced the expression of NLRP3-related inflammosome cytokines in human dendritic cells in vitro. They confirmed that dendritic cells hyperactivated by their adjuvant in vitro could activate T-cells, and using transwell plates evaluated their ability to migrate towards certain chemokines, mimicking dendrite migration to lymph nodes.
After more confirmatory studies in mice, Corner evaluated their compound’s ability to enhance the immune response during vaccination in mice and non-human primates, using influenza as a model vaccine and disease. In both model animal systems, they saw an increase in the immune response (B-cell secreted flu-specific antibodies, and T-cell secreted IFNγ) in animals that had received their adjuvant during vaccination, relative to vaccination alone. Taken together, they used these data to support further work in developing their lipid-based adjuvant program.
In the larger community context, Corner Therapeutics is part of an emerging NLRP3-modulatory cluster in Watertown. Corner is trying to stimulate NLRP3 pathways to improve the immunity generated by vaccines but across Arsenal Street, Neumora Therapeutics is developing an NLRP3 inhibitor as an alternative to semaglutide (Wegovy) for weight loss. Its interesting to see how a therapeutic in one context could potentially exacerbate disease in another. To end on a lighter note, we’re curious to see which company’s compound is more potent head to head in dedritic cells: Corner’s NLRP3 activator, or Neumora’s inhibitor?
That’s all for this week. We’ll be back next week with more life science news!
