Summary of Invention
This invention allows for the accurate synthesis of an effective vaccine adjuvant. Through structural, chemical , and in vitro biochemical and in vivo cellular assays, the investigators have identified cGAMP as a founding member of a family of metazoan 2’,5’-containing cyclic heterodinucleotide second messengers distinct from bacterial 3’,5’ cyclic dinucleotides (CDNs).
Until now, it had been assumed that metazoan cGAMP contained a pair of 3’,5’ linkages similar to protozoan CDNs. The inventors’ discovery that, in fact, cGAMP contains both a 2’,5’ linkage and a 3’,5’ linkage makes it possible to synthesize the correct version of cGAMP for use as an adjuvant in various vaccines and disease treatments.
cGAMP stimulates the production of type 1 interferon by binding and activating a protein called STING. STING then activates various protein kinases that induce interferons and cytokines. In this way, the cGAMP pathway plays a pivotal role in antiviral defense and immune responses.
This invention enables accurate laboratory synthesis of metazoan cGAMP, facilitating its use in a promising new class of vaccine adjuvants.
Adjuvants significantly enhance the immune response of a patient to a co-administered antigen, thereby enabling less potent or excessively costly antigens to be used or enhancing vaccination benefits for poor responders.
cGAMP has the potential for widespread use as an adjuvant in most infectious-disease and cancer vaccines. With global vaccine sales currently at ~$23 billion a year, there is significant market opportunity.
Areas of Application
Infectious-disease and cancer vaccines
Provisional Application 61/817,269 filed 04/29/2013; Provisional Application 61/817,369 filed 05/03/2013; Provisional Application 61/860,818 filed 06/31/2013; Provisional Application No. 62/010,044 filed on 06/10/2014
Dinshaw Patel, MD, Laboratory Head, Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering
Yashodhara Dash, MBBS, PhD, MBA
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