Available Technology
Bisphosphonates as novel adjuvants to enhance the adaptive immune response
Technology:
Novel adjuvant
Markets Addressed
Despite decades of adjuvant research, only four adjuvants have been approved in the seven major markets. Of these, only two (Alum and AS04) are licensed in the US. The availability of additional adjuvants has been minimized due to increased safety requirements imposed by the regulatory authorities. Although Alum is safe and efficacious in many prophylactic indications (particularly in those vaccines achieving protection through a strong Th2 response), it has proven unsuccessful in many indications. The development of novel adjuvants is therefore an area of high interest for many companies.
Small molecule adjuvants are pharmaceuticals included in vaccine preparations to enhance the immune response and protection generated by vaccination. The inventors present evidence that two bisphosphonates can stimulate the adaptive immune response against multiple types of antigens. This suggests that bisphosphonates may be useful as adjuvants in the development of novel vaccine preparations, and particularly beneficial for:
• Use with poorly immunogenic antigens. Increasingly, new infectious disease vaccines have moved away from whole cell/virus preparations toward individual non-infectious subunits. These preparations are safer, but less immunogenic. The inclusion of adjuvants may increase the potency of the immune response generated by vaccines containing these less immunogenic antigens.
• Use in patients with compromised immune systems. In elderly or other immune-compromised patients, immune responses to traditional vaccines can be muted. The addition of an adjuvant can increase the potency of immune responses in these patients.
• Use in vaccine preparation when antigen is difficult to produce. Some adjuvants can decrease the amount of antigen required to develop protection by vaccination. This may decrease the cost of vaccine production when an antigen is particularly expensive.
Innovations and Advantages
Despite decades of adjuvant research, only four adjuvants have been approved in the seven major markets. Of these, only two (Alum and AS04) are licensed in the US. The availability of additional adjuvants has been minimized due to increased safety requirements imposed by the regulatory authorities. Although Alum is safe and efficacious in many prophylactic indications (particularly in those vaccines achieving protection through a strong Th2 response), it has proven unsuccessful in many indications. The development of novel adjuvants is therefore an area of high interest for many companies.
Bisphosphonates are clinically approved and used extensively for the treatment of bone resorption diseases, such as osteoporosis. The von Andrian laboratory discovered a novel function for bisphosphonates by showing that they also enhance the adaptive immune response to a wide variety of antigens. Furthermore, bisphosphonates engage molecular pathways that are distinct from Toll-like receptor (TLR) agonists, such as AS04. Bisphosphonates may therefore be effective as novel adjuvants in vaccination, and have a straightforward path to the clinic.
To determine the mechanism of action of bisphosphonates on immune enhancement, the von Andrian laboratory investigated the effects of four specific bisphosphonates on immune cells. Their findings, summarized below, distinguish bisphosphonate adjuvant activity from that of other marketed and known adjuvants:
• Subcutaneous injection of bisphosphonate compounds increase antigen-specific B- and T- cell response to live viruses, inactive viruses, protein antigens and haptens (immunogenic small molecules). This effect was observed following administration of bisphosphonates prior (up to 60 days), concomitantly, or after (up to 4 days) immunization.
• Bisphosphonates increase the migration of dendritic cells from the site of injection to the local lymph nodes, increasing antigen presentation to B- and T- cells
• Immune enhancement by bisphosphonates occurs independently of the Myd88 adaptor protein, suggesting that bisphosphonate adjuvant activity is independent of the TLR signaling pathway.
Additional Information
This technology is available for worldwide, exclusive licensing and/or a collaborative research program with the von Andrian laboratory.
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Inventor(s):
Iannacone, Matteo
Moseman, Elliott Ashley
Tonti, Elena
von Andrian, Ulrich H.
Categories:
For further information, please contact:
Michal Preminger, Director of Business Development
(617) 432-0920
Reference Harvard Case #3845