Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

Autor: Andrea R Delpero, Larry Karnes, Shannon E. Ronca, Shashikant Nagre, David G. Alleva, Sarah S Webb, Hanne Andersen Elyard, Allison I Jasa, Thomas M. Lancaster, JoAnn Yee, Sylaja Murikipudi, Vidhya Rao, Frans Sollie, Nishit J Shah, Freedom M Green, Melanie M Scully, Jeffrey R Haworth, Thillainaygam Sathiyaseelan, Emma K Greaves, Ramya Ragupathy, Jeffrey Klein, Todd C. Zion
Rok vydání: 2021
Předmět:
medicine.medical_treatment
PFU
plaque-forming units
Antibodies
Viral
Immunoglobulin G
Neutralization
Mice
PRNT
plaque reduction neutralization test
Infectious disease
ID50
Inhibitory Dilution 50%
SP
Spike Protein
NHP
non-human primate
Immunogenicity
Titer
Infectious Diseases
Spike Glycoprotein
Coronavirus
Vaccines
Subunit
Molecular Medicine
APCs
antigen-presenting cells
Rabbits
EUA
Emergency Use Authorization
Adjuvant
Primates
COVID-19 Vaccines
Recombinant Fusion Proteins
Ag
antigen
MFI
mean fluorescent intensity
Biology
Article
Virus
nAb
neutralizing antibody
Neonatal Fc receptor
PRNT50
maximum dilution with greater than 50% inhibition
Antigen
ACE2
angiotensin converting enzyme-2
medicine
Animals
Fc-fusion
SP/RBD
spike protein receptor binding domain
Pandemic
General Veterinary
General Immunology and Microbiology
Prophylaxis
ELISA
Enzyme Linked Immunosorbent Assay
SARS-CoV-2
Public Health
Environmental and Occupational Health
COVID-19
Antibodies
Neutralizing
Virology
Coronavirus
HCS
Human convalescent serum
OD
optical density
P
passage
biology.protein
Zdroj: Vaccine
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2021.09.077
Popis: 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.
Databáze: OpenAIRE
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