January 7, 2026

Tolerance vaccines, also called inverse vaccines, are designed to increase immune tolerance for an antigen. It is important to note that a tolerance (inverse) vaccine has not yet been approved by the FDA. However, several are in pre-clinical and clinical trials.

Traditional vaccines normally contain a moiety that resembles a disease-causing virus or bacterial cell, its toxin, or one of its surface proteins. The moiety is encountered by an APC (antigen presenting cell) and the APC presents the moiety to CD4 and CD8 T cells to provoke an immune response. Eventually, hopefully, memory T and B cells are created for a long-lasting immune response.

However, tolerance vaccines need to activate the tolerance components of the immune system. Tolerance (inverse) vaccines need to be cleverly designed to target cells of the immune system involved in tolerance, or locations in the body known to have a preference for tolerance, for example, the skin and the liver. The liver’s microenvironment favors immune tolerance and can result in the generation of regulatory T cells (Tregs). If successful in targeting particular cells to generate a tolerance response, tolerance vaccines have the potential to treat allergies and autoimmune diseases.

However, there are various therapeutic modalities that can be leveraged in the immune tolerance space. For example, administration of tolerogenic dendritic cells (tolDCs) or the use of peptides on the surface of nanoparticles. Science for Bankers’ Modalities MasterClass covers all therapeutic modalities, providing the background required to fully understand the possible therapeutic modalities that can be leveraged to increase immune tolerance.