Antibodies specifically binding to Zika virus epitopes and uses thereof
Inventors
Assignees
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Publication Number
US-11912757-B2
Publication Date
2024-02-27
Expiration Date
Abstract
The invention relates to antibodies, and antigen binding fragments thereof, that potently neutralize infection of ZIKV. The invention also relates to antigenic sites to which the antibodies and antigen binding fragments bind, as well as to nucleic acids that encode and immortalized B cells that produce such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies and antibody fragments of the invention in screening methods as well as in the diagnosis, prophylaxis and treatment of ZIKV infection.
Core Innovation
The invention relates to antibodies and antigen-binding fragments thereof that specifically bind to a Zika virus EDIII epitope and are used for inhibiting a Zika virus infection in a subject. The antibodies are defined by particular CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences corresponding to specified SEQ ID NO sets, and embodiments include defined heavy-chain variable region and light-chain variable region sequences or sequence-identity constraints.
The invention further provides antibody embodiments with an Fc moiety and defines how Fc binding is reduced. Specific Fc moiety mutations, including CH2 L4A and CH2 L5A mutations and other listed Fc mutation sites, reduce binding to FcγRI, FcγRIIa, and FcγRIIIa or combinations thereof. The disclosed formats support inhibition of Zika virus infection through administration of the specified antibody or antigen-binding fragment.
Beyond infection inhibition, the document describes diagnostic use for Zika virus infection by targeting NS1. It includes a blockade-of-binding ELISA approach using NS1 serodiagnosis and labeled probe antibodies, along with discussion of NS1 antibody specificity and cross-reactivity for ZIKV versus DENV NS1.
Claims Coverage
The independent claims cover methods of inhibiting Zika virus infection using EDIII epitope-binding antibodies, antibody embodiments that specifically bind a Zika virus EDIII epitope, and antibody sequence definitions and Fc moiety mutations that reduce Fc receptor binding. Across the independent claims, the inventive features include defined CDR sequence sets for EDIII epitope binding, optional or required Fc mutations that reduce FcγR binding, and specified VH/VL requirements using SEQ ID NO:26 and SEQ ID NO:27 or identity constraints.
Cdr sequence sets binding to zika virus ediii epitope
An antibody or antigen-binding fragment that specifically binds to a Zika virus EDIII epitope, wherein the antibody comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences of either SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, EDN, and SEQ ID NO: 25, respectively, or SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, and SEQ ID NO: 25, respectively.
Fc moiety reduces binding to Fcγ receptors
An antibody or antigen-binding fragment that specifically binds to a Zika virus EDIII epitope, wherein the antibody comprises an Fc moiety comprising a mutation at at least one of E233-G236, P238, D265, N297, A327, P329, D270, Q295, R292, S239, E269, E293, Y296, V303, P331, K338, D376, and K414, wherein the mutation reduces binding of the antibody or antigen-binding fragment to an FcγRI, an FcγRIIa, an FcγRIIIa, or any combination thereof.
Ch2 l4a and/or ch2 l5a Fc mutations
An antibody or antigen-binding fragment that specifically binds to a Zika virus EDIII epitope, wherein the antibody comprises an Fc moiety that comprises a CH2 L4A mutation, a CH2 L5A mutation, or both.
Defined vh and vl sequences (seq id no:26 and seq id no:27)
An antibody or antigen-binding fragment that specifically binds to a Zika virus EDIII epitope, wherein the antibody comprises the heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 26 and the light chain variable region (VL) amino acid sequence of SEQ ID NO: 27.
Overall, the independent claims define EDIII epitope-binding antibodies by specific CDRH/CDRL sequence sets, and in some claims require Fc moiety mutations that reduce binding to FcγRI, FcγRIIa, and FcγRIIIa and/or specify the VH/VL sequences SEQ ID NO:26 and SEQ ID NO:27.
Stated Advantages
Inhibiting a Zika virus infection in a subject.
Reducing binding of an antibody or antigen-binding fragment to FcγRI, FcγRIIa, FcγRIIIa, or any combination thereof via specified Fc moiety mutations.
Providing Zika virus NS1 serodiagnosis using a blockade-of-binding ELISA approach.
Documented Applications
Therapeutic use for inhibiting Zika virus infection in a subject by administering an EDIII epitope-binding antibody or antigen-binding fragment.
Diagnostic use for Zika virus infection via NS1 serodiagnosis using an ELISA blockade-of-binding assay with labeled probe antibodies.
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