| Institution: | 1. Akston Biosciences Corporation., 100 Cummings Center, Suite 454C, Beverly, MA 01915, United States;2. Biomere Biomedical Research Models, 57 Union St., Worcester, MA 01608, United States;3. Feigin ABSL-3 Facility, Baylor, College of Medicine, 1102 Bates Ave, 300.15, Houston, TX 77030, United States;4. BIOQUAL, Inc., 9600 Medical Center Drive, Suite 101, Rockville, MD 20850-3336, United States;5. Primate Assay Laboratory, CA National Primate Research Center, University of California, Davis, CA 95616, United States;6. Sinclair Research Center, 562 State Road DD, Auxvasse, MO 65231, United States;7. Pharmaceutical Research Associates Group B.V., Amerikaweg 18, 9407 TK Assen, Netherlands |
| Abstract: | AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide? ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain. |
