Description:
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
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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.
