tetano
Editor, Senior Moderator
Vaccine
. 2021 Oct 5;S0264-410X(21)01294-9.
doi: 10.1016/j.vaccine.2021.09.077. Online ahead of print.
Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS-452
David G Alleva[SUP] 1 [/SUP], Andrea R Delpero[SUP] 1 [/SUP], Melanie M Scully[SUP] 1 [/SUP], Sylaja Murikipudi[SUP] 1 [/SUP], Ramya Ragupathy[SUP] 1 [/SUP], Emma K Greaves[SUP] 1 [/SUP], Thillainaygam Sathiyaseelan[SUP] 1 [/SUP], Jeffrey R Haworth[SUP] 1 [/SUP], Nishit J Shah[SUP] 1 [/SUP], Vidhya Rao[SUP] 1 [/SUP], Shashikant Nagre[SUP] 1 [/SUP], Thomas M Lancaster[SUP] 1 [/SUP], Sarah S Webb[SUP] 2 [/SUP], Allison I Jasa[SUP] 2 [/SUP], Shannon E Ronca[SUP] 3 [/SUP], Freedom M Green[SUP] 3 [/SUP], Hanne Andersen Elyard[SUP] 4 [/SUP], JoAnn Yee[SUP] 5 [/SUP], Jeffrey Klein[SUP] 6 [/SUP], Larry Karnes[SUP] 6 [/SUP], Frans Sollie[SUP] 7 [/SUP], Todd C Zion[SUP] 8 [/SUP]
Affiliations
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.
Keywords: COVID-19; Coronavirus; Fc-fusion; Infectious disease; Pandemic; Prophylaxis.
. 2021 Oct 5;S0264-410X(21)01294-9.
doi: 10.1016/j.vaccine.2021.09.077. Online ahead of print.
Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS-452
David G Alleva[SUP] 1 [/SUP], Andrea R Delpero[SUP] 1 [/SUP], Melanie M Scully[SUP] 1 [/SUP], Sylaja Murikipudi[SUP] 1 [/SUP], Ramya Ragupathy[SUP] 1 [/SUP], Emma K Greaves[SUP] 1 [/SUP], Thillainaygam Sathiyaseelan[SUP] 1 [/SUP], Jeffrey R Haworth[SUP] 1 [/SUP], Nishit J Shah[SUP] 1 [/SUP], Vidhya Rao[SUP] 1 [/SUP], Shashikant Nagre[SUP] 1 [/SUP], Thomas M Lancaster[SUP] 1 [/SUP], Sarah S Webb[SUP] 2 [/SUP], Allison I Jasa[SUP] 2 [/SUP], Shannon E Ronca[SUP] 3 [/SUP], Freedom M Green[SUP] 3 [/SUP], Hanne Andersen Elyard[SUP] 4 [/SUP], JoAnn Yee[SUP] 5 [/SUP], Jeffrey Klein[SUP] 6 [/SUP], Larry Karnes[SUP] 6 [/SUP], Frans Sollie[SUP] 7 [/SUP], Todd C Zion[SUP] 8 [/SUP]
Affiliations
- PMID: 34642088
- DOI: 10.1016/j.vaccine.2021.09.077
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.
Keywords: COVID-19; Coronavirus; Fc-fusion; Infectious disease; Pandemic; Prophylaxis.