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 immune-mediated 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.
The field of tolerogenic adjuvants is still in its infancy. No compounds have been licensed yet in the U.S. and immune-mediated diseases continue to be treated mostly with broadly immunosuppressive drugs or long-term single or multi-allergen immunotherapy. In contrast to drugs, tolerogenic or immunomodulatory adjuvants would interfere with immune responses to specific antigens through a variety of mechanisms including the induction of regulatory T cells, or by changing the profile of the pathogenic lymphocyte response (e.g., Th1/Th2/Th17, etc).
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 for 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., acellular pertussis vaccine, influenza, etc.), and development of vaccines for: emerging threats (e.g., Ebola outbreaks); 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). Examples of applications of tolerogenic adjuvants include: combination with allergen immunotherapy to accelerate tolerance induction, increase the magnitude of tolerance and decrease treatment duration; and combination with self- or donor-derived antigens to induce tolerance in the recipient.
Project Goal
The objective of this program is to support the screening for new adjuvant candidates for vaccines against infectious diseases or for immune-mediated diseases (autoimmune and allergic diseases or transplant tolerance); adjuvant characterization; and early-stage optimization.
Phase I Activities 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 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 testing of newly identified immunomodulatory compounds or formulations as stand-alone immunotherapeutics (i.e., without a specific antigen)
• The testing of newly identified immunomodulatory compounds or formulations in cancer models
• The further development of previously identified adjuvants, if being used for the original indication (i.e., in vaccines against infectious diseases or as a tolerogenic adjuvant)
• The conduct of clinical trials (see https://osp.od.nih.gov/wp-content/uploads/2014/11/NIH%20Definition%20of%20Clinical%20Trial%2010-23-2014-UPDATED_0.pdf for the NIH definition of a clinical trial)
