Human antibodies to Crimean Congo Hemorrhagic Fever Virus
The present disclosure is directed to antibodies binding to and neutralizing Crimean Congo Hemorrhagic Fever Virus and methods for use thereof.
1 . A method of detecting a Crimean Congo Hemorrhagic Fever Virus infection in a subject comprising:
(a) contacting a sample from said subject with an antibody or antigen binding fragment thereof comprising heavy and light chain CDR sequences comprising SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively; and
(b) detecting Crimean Congo Hemorrhagic Fever Virus in said sample by binding of said antibody or antibody fragment to a Crimean Congo Hemorrhagic Fever Virus antigen in said sample.
2 . A method of treating a subject infected with Crimean Congo Hemorrhagic Fever Virus or reducing the likelihood of infection of a subject at risk of contracting Crimean Congo Hemorrhagic Fever Virus, comprising delivering to said subject an antibody or antigen binding fragment thereof comprising heavy and light chain CDR sequences comprising SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively.
3 . The method of claim 2 , wherein the antibody or antigen binding fragment thereof is encoded by heavy and light chain variable regions comprising SEQ ID NOS: 85 and 86, respectively.
4 . The method of claim 2 , wherein the antibody or antigen binding fragment thereof is encoded by heavy and light chain variable regions having 95% identity to heavy and light chain variable sequences comprising SEQ ID NOS: 85 and 86, respectively, wherein the heavy and light chain CDRs comprise SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively.
5 . The method of claim 2 , wherein said antibody or antigen binding fragment thereof is encoded by heavy and light chain variable regions having 90% identity to SEQ ID NOS: 85 and 86, respectively, wherein the heavy and light chain CDRs comprise SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively.
6 . The method of claim 2 , wherein said antibody or antigen binding fragment thereof comprises heavy and light chain variable regions comprising SEQ ID NOS: 185 and 186, respectively.
7 . The method of claim 2 , wherein said antibody or antigen binding fragment thereof comprises heavy and light chain variable regions comprising 90% identity to SEQ ID NOS: 185 and 186, respectively, wherein the heavy and light chain CDRs comprise SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively.
8 . The method of claim 2 , wherein said antibody or antigen binding fragment thereof comprises heavy and light chain variable regions comprising 95% identity to SEQ ID NOS: 185 and 186, respectively, wherein the heavy and light chain CDRs comprise SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively.
9 . The method of claim 2 , wherein said antibody is a chimeric antibody or a bispecific antibody, or wherein the antigen binding fragment thereof is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2 fragment, or Fv fragment.
10 . The method of claim 2 , wherein said antibody is an IgG, or a recombinant IgG antibody or antigen binding fragment thereof comprising an Fc portion mutated to eliminate or enhance FcR interactions compared to wild-type, to increase half-life and/or increase therapeutic efficacy compared to wild-type, or glycan modified to eliminate or enhance FcR interactions compared to wild-type.
11 . The method of claim 2 , wherein said antibody or antigen binding fragment thereof is administered prior to infection.
12 . The method of claim 2 , wherein said antibody or antigen binding fragment thereof is administered after infection.
13 . The method of claim 2 , wherein said subject is a pregnant female, a sexually active female, or a female undergoing fertility treatments.
14 . The method of claim 2 , wherein delivering comprises antibody or antigen binding fragment thereof administration, or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen binding fragment thereof.
15 . A monoclonal antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises heavy and light chain CDR sequences comprising SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively, wherein said antibody is a recombinant IgG antibody or antibody fragment comprising an Fc portion mutated to eliminate or enhance FcR interactions compared to wild-type, to increase half-life and/or increase therapeutic efficacy compared to wild-type, or glycan modified to eliminate or enhance FcR interactions compared to wild-type.
16 . A hybridoma or engineered cell comprising one or more nucleic acid segments encoding an antibody or antigen binding fragment thereof wherein the antibody or antibody fragment comprises heavy and light chain CDR sequences comprising SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively.
17 . A vaccine formulation comprising antibodies or antigen binding fragments thereof comprising heavy and light chain CDR sequences comprising SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively, wherein said antibodies are recombinant IgG antibodies or antibody fragments comprising an Fc portion mutated to eliminate or enhance FcR interactions compared to wild-type, to increase half-life and/or increase therapeutic efficacy compared to wild-type, or glycan modified to eliminate or enhance FcR interactions compared to wild-type.
18 . A method of determining the antigenic integrity or correct conformation of a Crimean Congo Hemorrhagic Fever Virus antigen comprising:
(a) contacting a sample comprising said antigen with an antibody or antigen binding fragment thereof comprising heavy and light chain CDR sequences comprising SEQ ID NOS: 330, 331, and 332, and SEQ ID NOS: 480, 481 and 482, respectively; and
(b) determining antigenic integrity or correct conformation of said antigen by detectable binding of said antibody or antibody fragment to said antigen.
19 . The method of claim 10 , wherein said Fc portion mutated to eliminate or enhance FcR interactions compared to wild-type, to increase half-life and/or increase therapeutic efficacy compared to wild-type is a LALA, LALA PG, N297, GASD/ALIE, DHS, YTE or LS mutation.
20 . The method of claim 10 , wherein the antibody is glycan modified by enzymatic or chemical addition or removal of glycans or expressed in a cell line engineered with a defined glycosylating pattern.