February 23, 2022
National Institute of Allergy and Infectious Diseases (NIAID)
The National Institute of Allergy and Infectious Diseases (NIAID) is interested in supporting preclinical studies utilizing animal models or human tissue specimens that focus on 1) optimizing treatment and graft monitoring to reduce incidence of acute rejection and maximize graft survival after vascularized composite allotransplantation (VCA) and 2) minimizing immunosuppression required for long-term VCA acceptance.
VCA involves transplantation of a vascularized human body part containing multiple tissues as a functional unit. VCA differs from traditional solid organ transplantation (SOT) in that it is not considered a life-saving procedure, but rather as a life-enhancing procedure. VCA holds great promise for the restoration of tissue integrity and sensory function after traumatic tissue loss. Yet, to justify widespread clinical adoption, recipient morbidity and immunosuppression must be minimized without exacerbating or stimulating alloimmunity.
The first successful VCA procedures were performed in France, a hand transplant in 1998, and subsequently a face transplant in 2005. Since then, approximately 47 face transplants and 130 hand transplants, as well as other VCA procedures, have been performed world-wide. Clinical VCA treatment strategies are based on solid organ transplant protocols and require lifelong immunosuppression that is associated with systemic toxicities and increased susceptibility to cancer, infectious disease, and cardiovascular and renal complications. Additionally, data from the International Registry on Hand and Composite Tissue Transplantation reveal an 80% incidence of acute rejection after VCA, attesting to the high immunogenicity of these allografts and the fact that optimal immunosuppressive regimens have not been achieved.
Over the past the 20 years, VCA model development, preservation techniques, and early graft survival have progressed substantially due largely to Department of Defense program funding initiated in 2012. The field is now well-positioned to build on this progress by developing VCA-optimized immunosuppression protocols and examining in detail the immunologic barriers to graft acceptance and tolerance that are either unique to VCA, or common to multiple types of allogeneic transplants.
The objective of this Notice of Special Interest (NOSI) is to encourage preclinical research in animal models of VCA or human composite tissue specimens that focus on 1) understanding immune mechanisms of rejection and tolerance and 2) the development of therapeutic and monitoring approaches that address the unique vulnerabilities and opportunities of face, limb, and abdominal wall vascularized composite allografts. The overarching goal is to expand clinical opportunities and improve outcomes for these life-enhancing procedures.
Research Objectives and Scope
This NOSI will support applications that use human specimens and/or rodent, porcine, or nonhuman primate transplant models to develop novel therapeutic approaches to reduce acute rejection and maximize VCA survival and/or minimize immunosuppression required for long-term VCA acceptance. In addition to immunologic assays, an assessment of strength or weightbearing ability (if applicable), nerve regeneration, and susceptibility/resistance to infection may be appropriate. Incorporation of cutting-edge technologies and interdisciplinary collaborations are encouraged to adequately address the immunological and physiological complexities of these multi-component grafts.
Research areas supported by this NOSI include, but are NOT limited to:
This NOSI will NOT support:
Application and Submission Information
This notice applies to due dates on or after June 5, 2022 and subsequent receipt dates through May 7, 2026.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Financial/Grants Management Contact(s)