Currently, for infectious diseases, five adjuvants have been used in vaccines licensed in the United States (U.S.): Aluminum hydroxide/aluminum phosphate; AS04, which consists of 4’-monophosphoryl lipid A (MPL) and aluminum hydroxide; AS01B, a liposomal formulation of MPL and QS-21; MF59, an oil-in-water emulsion; and CpG 1018, a CpG Oligodinucleotide. No adjuvanted vaccines have been approved by the FDA to treat/prevent immune-mediated diseases; thus, treatment for these diseases continue to be comprised mostly of broadly immunosuppressive drugs or long-term single- or multi-allergen immunotherapy.
The goal of the adjuvant development programs is to establish and expand the availability of novel vaccine adjuvants that researchers can use for preclinical vaccine development in both infectious and immune-mediated diseases. Adjuvant development is supported through the following NIAID mechanisms:
- The Adjuvant Development BAA program launched in 2008 and reissued in 2013 and 2018 to advance research of adjuvant development. The Adjuvant Development SBIR program started in 2017 to engage the small business community, and is re-issued annually as part of PHS’s omnibus solicitation.
- The Production of Adjuvant Mimics program began in 2020 and re-issued annually as part of the Small Business Innovation Research initiative to address the limited availability of adjuvants at an advanced stage of development for use in vaccine development and preclinical research. The program supports the development, commercialization, and distribution of adjuvants that mimic the function of existing adjuvants with a proven track record in clinical and late-stage pre-clinical studies.
- The Advancing Vaccine Adjuvant Research for Tuberculosis (TB) (AVAR-T) program (planned award Fall 2022) involves the identification of the optimal formulations of adjuvant-TB vaccine/immunogens through side-by-side testing to assess the safety, immunogenicity, immune profiles, and efficacy of vaccine candidates in comparison with BCG.
- NIAID accepts Investigator-initiated Grants focused on adjuvant development in response to NIAID’s parent announcements for R-type grants.
Several adjuvants that resulted from NIAID adjuvant development grants and contracts are accessible through the NIAID Vaccine Adjuvant Compendium (VAC).
Main Areas of Focus
- Preclinical development of novel adjuvants coupled with antigens, including mechanistic analyses of the novel adjuvant/antigen combinations
- Formulation and stability studies
- Optimization of immunization regimens and delivery routes
- Toxicology testing
- Pharmacokinetics/absorption, distribution, metabolism, and excretion studies
- Clinical good manufacturing processes (cGMP) production