Fast-Track proposals will be accepted Direct-to-phase II proposals will be accepted Number of anticipated awards: 1-3 Mission: BioD COR: Wolfgang Leitner Budget (total costs): Phase I: $300,000/year for up to 2 years Phase II: $1,000,000/year with appropriate justification by the applicant for up to 3 years Background The goal of this program is to support 1) the screening for new vaccine adjuvant candidates against infectious diseases or for tolerogenic adjuvants for the treatment of autoimmune or allergic diseases, or 2) the down-selection of adjuvants to support the subsequent development of novel adjuvanted vaccines. For the purpose of this SBIR, the definition of vaccine adjuvants follows that of the U.S. Food and Drug Administration (FDA): “Agents added to, or used in conjunction with, vaccine antigens to augment or potentiate and possibly target the specific immune response to the antigen.” Tolerogenic adjuvants are defined as compounds that promote immunoregulatory or immunosuppressive signals to induce nonresponsiveness to self-antigens in autoimmune diseases or transplantation, or environmental antigens in allergic diseases. Currently, only a few adjuvants other than aluminum salts (“Alum”) have been licensed in the United States (U.S.) as components of vaccines against infectious diseases. In addition, adjuvants may facilitate the development of Page 114 immunotherapeutics for immune-mediated diseases (e.g., allergic rhinitis, asthma, food allergy, autoimmunity, transplant rejection). The field of tolerogenic adjuvants is still in its infancy and no adjuvanted vaccines have been licensed yet in the U.S. In contrast to drugs that are primarily used for treatment, tolerogenic or immunomodulatory adjuvants may regulate immune responses to specific antigens through a variety of mechanisms, including induction of regulatory T cells or alterations in the profile of the pathogenic lymphocyte response (e.g., Th1 to Th2 or vice versa). For tolerogenic and immune modifying adjuvants, the antigens may originate from environmental (allergy) or endogenous (autoimmunity) sources and may not need to be supplied exogenously together with the adjuvant. When pursuing this approach, the proposal must describe a compelling mechanism by which the adjuvant would modulate an antigen-specific response and include studies demonstrating altered or suppressed responses against the allergen or autoantigen. Advances in understanding of innate immune mechanisms continue to lead to new putative targets for vaccine adjuvants and for immunotherapy. Simultaneously, progress is being made in the identification of in vitro correlates of clinical adjuvanticity, which allows the design of in vitro screening assays to discover novel adjuvant candidates in a systematic manner. The gaps that need to be addressed by new adjuvants include improvements to existing vaccines (e.g., the acellular pertussis vaccine, influenza, etc), and development of vaccines for: emerging and re-emerging threats (e.g., Coronaviruses, Enteroviruses, MRSE); special populations that respond poorly to existing vaccines (e.g., elderly, newborns/infants, immunosuppressed patients); or treatment/prevention of immune-mediated diseases (e.g., allergic rhinitis, asthma, food allergy, autoimmunity, transplant rejection). For example, the combination of putative tolerogenic adjuvants with allergen immunotherapy should aim at accelerating tolerance induction, increasing the magnitude of tolerance and decreasing treatment duration. For transplantation, donor-derived major and minor histocompatibility molecules that are not matched between donor and recipient may be formulated with novel tolerogenic adjuvants and used to induce transplant tolerance in the recipient. In addition to the need for novel adjuvants, there is a need to identify the most suitable adjuvant for a novel vaccine candidate. Adjuvants are frequently selected purely based on availability, rather than as a result of systematic side-by-side comparisons of candidates to determine which adjuvant-antigen combination induces the most desirable response. This solicitation supports studies to down-select a lead adjuvant-antigen combination to generate the data for a subsequent vaccine development effort.