Self-Assembling Vaccine Platform: Low-Cost, Highly Scalable Manufacturing, Rapid Deployment of Vaccines to Combat COVID Variants and Emerging Infectious Diseases

Innovative technologies are needed to develop therapeutics to protect against rapidly emerging infectious diseases such as variants of SARS-CoV-2 virus, Mpox virus, Respiratory Syncytial Virus, and influenza virus. Peptide vaccines have many advantages over traditional platforms such as live attenuated, inactivated, subunit, mRNA, or viral vectored vaccines. Because of their smaller size, they usually require covalently coupling to a hapten carrier protein such as Diphtheria toxoid to induce a robust immune response. The vaccine technology platform we have developed is a peptide-based self-assembling scaffold to which antigenic peptides can be covalently attached to create a highly antigenic vaccine against functionally critical proteins of a pathogen (e.g., Spike glycoprotein of SARS-CoV-2, Hemagglutinin of Influenza, etc.). Advantages of our vaccine platform include: (1) completely synthetic chemical manufacturing (no biological organisms required); (2) massive scalability of ~500 kg in 6 months; (3) safe due to the lack of viral or endotoxin bioburden contamination; (4) more cost-effective than traditional and mRNA vaccine platforms (5) very stable when lyophilized; (6.) our vaccine is non-infectious and non-replicating, making the immune response more reproducible. We previously constructed a SARS-CoV-2 vaccine containing three S-protein peptides that was robust and durable to 6 months. In live virus challenge studies, the immunized mice were protected well against mortality although some morbidity was observed. The objectives of this proposal are to use our peptide scaffold platform to construct novel pan-SARS-CoV-2 VOC and an Omicron variant-specific vaccine that we predict will induce a robust and durable immune response that protects against virus induced morbidity and mortality. For the pan-vaccine, peptides were selected from highly conserved regions of the S-protein that are known to be functionally critical. Three of these peptides will be separately conjugated to our self-assembling scaffold and then mixed to form a trivalent vaccine. Vaccines will be functionally tested in mouse immunization and hamster live virus animal challenge studies to measure protection. Following the mouse and hamster studies, an IND-enabling GLP rabbit safety study will be started while IND-enabling stability and CMC studies are ongoing. Following data compilation and writing, the IND will be submitted to the FDA and cGMP manufacturing of the vaccines will begin. Once enough material is available, cGMP/GLP compliant fill/finish protocols will be optimized to produce several thousand cGMP vaccine doses for future human Phase 1 Clinical Trials in collaboration with MAJ Michael Koren, M.D., Director of the WRAIR Clinical Trial Center. Although clinical trials are outside the scope of this proposal, Hexamer and 12 congressional supporters are currently working to secure Congressionally Directed Spending in FY2024 for human clinical trials following the IND submission in this proposal. Another important objective of our proposal is to use the previously acquired data as a template to design and produce other protective infectious disease vaccines of interest to the U.S. military. GMP scaffold will be provided to WRAIR and other military institutes for their vaccine design applications addressing other infectious disease indications of importance to homeland security and the U.S. military. The advantages of our novel synthetic peptide-based scaffold as a peptide vaccine are directly relevant for the military to produce vaccines to infectious diseases or bioterrorism threats that could compromise the health of military personnel, their families, allies, and the public. We intend on providing as much input and advice that the U.S. military requests about our technology, and we will assist with the design, construction, and preclinical and clinical testing. Less