Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS-452. Issue 45 (29th October 2021)

• Record Type: Journal Article
• Authors: Alleva, David G.; Delpero, Andrea R.; Scully, Melanie M.; Murikipudi, Sylaja; Ragupathy, Ramya; Greaves, Emma K.; Sathiyaseelan, Thillainaygam; Haworth, Jeffrey R.; Shah, Nishit J.; Rao, Vidhya; Nagre, Shashikant; Lancaster, Thomas M.; Webb, Sarah S.; Jasa, Allison I.; Ronca, Shannon E.; Green, Freedom M.; Elyard, Hanne Andersen; Yee, JoAnn; Klein, Jeffrey; Karnes, Larry; Sollie, Frans; Zion, Todd C.
• Is Part Of: Vaccine. Volume 39:Issue 45(2021)
• Page Start: 6601
• Page End: 6613
• Publication Date: 2021-10-29
• Subjects: Infectious disease -- Coronavirus -- Prophylaxis -- Pandemic -- COVID-19 -- Fc-fusion; ACE2 angiotensin converting enzyme-2 -- Ag antigen -- APCs antigen-presenting cells -- ELISA Enzyme Linked Immunosorbent Assay -- EUA Emergency Use Authorization -- HCS Human convalescent serum -- ID50 Inhibitory Dilution 50% -- MFI mean fluorescent intensity -- nAb neutralizing antibody -- NHP non-human primate -- OD optical density -- P passage -- PFU plaque-forming units -- PRNT plaque reduction neutralization test -- PRNT50 maximum dilution with greater than 50% inhibition -- SP Spike Protein -- SP/RBD spike protein receptor binding domain; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.09.077
• Languages: English
• ISSNs: 0264-410X

Abstract

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.