Fast-Track proposals will be accepted. Direct-to-phase II proposals will be accepted. Number of anticipated awards: 3-5 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. Page 111 Background Many experimental and licensed vaccines depend on adjuvants to exert their protective effect. While several immunostimulatory compounds and formulations are available commercially for use in preclinical studies, these compounds generally cannot be advanced into clinical trials. Furthermore, head-to-head comparisons of novel experimental and existing adjuvants is hampered by limited availability of such reagents. NIAID supports the discovery and development of novel adjuvants through different mechanisms, and this Funding Opportunity Announcement (FOA) is intended to address the limited availability of adjuvants that: mimic those with a favorable clinical track record; or show high potential in late preclinical testing. Program Goal Development, validation and production of adjuvants that are based on, or similar to, compounds or formulations previously successfully used in clinical trials, for use by the broader research community, either as commercial products or through licensing agreements. Phase I Activities must include at least the following 2 activities: • Development of one or more adjuvants (or adjuvant combinations)/adjuvant formulations that are based on, or similar to, an adjuvant with a proven clinical track record of high adjuvanticity; and • Preclinical testing to assure immune potency and safety. Immune potency studies shall include comparison to at least one well-established reference adjuvant that is expected to be effective in the disease model under study. Phase II Activities include, but are not limited to: • Establishment of an immunological profile of the lead product; • Pharmacological and toxicological studies in appropriate animal models; • Product validation, that includes in vitro and in vivo approaches using a relevant disease model; • Production scale-up; and • Development of a marketing plan. This SBIR will not support • Development of aluminum-based adjuvants as marketable products, unless the aluminum-component is used as a coadjuvant or carrier; • Discovery of novel immunostimulatory compounds; • Commercial development of adjuvants that do not have the ability or potential to activate human immune cells; • Development of adjuvant mimics that would violate existing patents; • Data analyses, pattern discovery from aggregated datasets; or • Development of AS01 biosimilars without previous consultation with NIAID. Intellectual Property: The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the awardee to perform the project. Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.