An Antibody from Single Human VH-rearranging Mouse Neutralizes All SARS-CoV-2 Variants Through BA.5 by Inhibiting Membrane Fusion.
A research team from the US has announced a mouse model used to generate a VH1-2 heavy chain (HC)- and Vκ1-33 light chain (LC)-based recombinant antibody that broadly neutralized all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including the newly emergent Omicron sub-variant BA.5.
Human monoclonal antibodies derived from B cells of patients infected from the early SARS-CoV-2 variants and from vaccinated individuals are rapidly losing their efficacy with the emergence of new Omicron sub-variants. The SARS-CoV-2 spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell surface. The spike protein is made of non-covalently linked subunits S1, which contains the receptor binding domain (RBD), and S2, which anchors the spike protein and forms the fusion pore after spike protein cleavage.
Humanized mice carrying immunoglobulin genes have earlier yielded monoclonal antibodies that successfully neutralized some of the SARS-CoV-2 variants but have not been developed to yield antibodies that neutralize the Omicron sub-variants.
The present study reports the generation of a broadly neutralizing monoclonal antibody developed using a humanized mouse model carrying single VH1-2 heavy chain (HC) and Vκ1-33 light chain (LC) segments. The SP1-77 antibody differs from previous monoclonal antibodies in the mechanism of SARS-CoV-2 inhibition, as well as the SARS-CoV-2 RBD epitope of binding. The researchers have established a successful prototype for using humanized mouse models carrying VH and Vκ segments to generate a diversity of antibodies and demonstrated the potential of using mouse models to develop humanized antibodies against various pathogens.
PS: Pls see another update below on another set of antibodies discovered by an Israeli team.
A research team from the US has announced a mouse model used to generate a VH1-2 heavy chain (HC)- and Vκ1-33 light chain (LC)-based recombinant antibody that broadly neutralized all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including the newly emergent Omicron sub-variant BA.5.
Human monoclonal antibodies derived from B cells of patients infected from the early SARS-CoV-2 variants and from vaccinated individuals are rapidly losing their efficacy with the emergence of new Omicron sub-variants. The SARS-CoV-2 spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell surface. The spike protein is made of non-covalently linked subunits S1, which contains the receptor binding domain (RBD), and S2, which anchors the spike protein and forms the fusion pore after spike protein cleavage.
Humanized mice carrying immunoglobulin genes have earlier yielded monoclonal antibodies that successfully neutralized some of the SARS-CoV-2 variants but have not been developed to yield antibodies that neutralize the Omicron sub-variants.
The present study reports the generation of a broadly neutralizing monoclonal antibody developed using a humanized mouse model carrying single VH1-2 heavy chain (HC) and Vκ1-33 light chain (LC) segments. The SP1-77 antibody differs from previous monoclonal antibodies in the mechanism of SARS-CoV-2 inhibition, as well as the SARS-CoV-2 RBD epitope of binding. The researchers have established a successful prototype for using humanized mouse models carrying VH and Vκ segments to generate a diversity of antibodies and demonstrated the potential of using mouse models to develop humanized antibodies against various pathogens.
PS: Pls see another update below on another set of antibodies discovered by an Israeli team.
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