Description:
Fast-Track proposals will be accepted.
Direct-to-phase II proposals will be accepted.
Number of anticipated awards: 1-3
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 the screening for new vaccine adjuvant candidates against infectious diseases or for
tolerogenic adjuvants for the treatment of autoimmune or allergic diseases. 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
non-responsiveness 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 as components of vaccines in the
United States (U.S.): 4’-monophosphoryl lipid A (MPL), adsorbed to alum as an adjuvant for an HPV vaccine; MPL and
QS-21 combined in a liposomal formulation for a varicella vaccine; CpG Oligodinucleotide as an adjuvant for a recombinant
Hepatitis B vaccine; and the oil-in-water emulsion MF59 as part of an influenza vaccine for people age 65 years and older.
In addition, adjuvants may facilitate the development of 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. No
compounds have been licensed yet in the U.S. and immune-mediated diseases are treated mostly with broadly
immunosuppressive drugs or long-term single- or multi-allergen immunotherapy. In contrast to drugs, tolerogenic or
immunomodulatory adjuvants may regulate immune responses to specific antigens through a variety of mechanisms,
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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.
Recent advances in understanding of innate immune mechanisms have led 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.
Program Goal
The objective of this program is to support the screening for new adjuvant candidates for vaccines against infectious
diseases, or for autoimmune and allergic diseases, or transplantation; their characterization; and early-stage optimization.
Phase I Activities may include, but are not limited to:
• Optimize and scale-up screening assays to identify new potential vaccine- or tolerogenic adjuvant candidates
• Create targeted libraries of putative ligands of innate immune receptors
• Conduct pilot screening assays to validate high-throughput screening (HTS) approaches for identifying adjuvant
candidates
• Develop or conduct in silico screening approaches to pre-select adjuvant candidates for subsequent in vitro screens and
validation
Phase II Activities may include, but are not limited to:
• HTS of compound libraries and confirmation of adjuvant activity of lead compounds
• Confirmatory in vitro screening of hits identified by HTS or in silico prediction algorithms
• Optimization of lead candidates identified through screening campaigns through medicinal chemistry or formulation
• Screening of adjuvant candidates for their usefulness in vulnerable populations, such as the use of cells from cord blood
of infants or elderly/frail humans
• Screening of adjuvant candidates in animal models representing vulnerable human populations
This SBIR will not support:
• The development of immunostimulatory compounds or formulations as stand-alone immunotherapeutics (i.e., without a
specific antigen/pathogen-specific vaccine component) unless the putative adjuvant is used to modulate or suppress the
response against an allergen or autoantigen. In this case, the proposal must include assays to demonstrate the effect of
the treatment with an adjuvant on specific allergens or autoantigens.
• The testing of newly identified immunomodulatory compounds or formulations in cancer models
• The further development of previously identified adjuvants
• The conduct of clinical trials (see https://grants.nih.gov/policy/clinical-trials/definition.htm for the NIH definition of a
clinical trial)
