Negative Vaccination Strategies for Promotion of Transplant Tolerance

Author:

Tunbridge Matthew J.12,Luo Xunrong2,Thomson Angus W.34

Affiliation:

1. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.

2. Department of Medicine (Nephrology), Duke University Medical Center, Durham, NC.

3. Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA.

4. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Abstract

Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without compromising host responses to infection or enhancing the risk of malignant disease is a major goal in transplantation. One promising approach to achieve this goal is based on the concept of “negative vaccination.” Vaccination (or actively acquired immunity) involves the presentation of both a foreign antigen and immunostimulatory adjuvant to the immune system to induce antigen-specific immunity. By contrast, negative vaccination, in the context of transplantation, involves the delivery of donor antigen before or after transplantation, together with a “negative adjuvant” to selectively inhibit the alloimmune response. This review will explore established and emerging negative vaccination strategies for promotion of organ or pancreatic islet transplant tolerance. These include donor regulatory myeloid cell infusion, which has progressed to early-phase clinical trials, apoptotic donor cell infusion that has advanced to nonhuman primate models, and novel nanoparticle antigen-delivery systems.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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