Arenavirus monoclonal antibodies and uses
Disclosed herein are compositions comprising arenavirus monoclonal antibodies, as well as therapeutic, diagnostic, and preventative methods using the novel antibodies. Preventative methods include preparation of vaccines, as well as factors (e.g. small molecules, peptides) that inhibit Old World arenavirus infectivity, including LASV and LCMV. In some embodiments, the antibodies provide pan-arenavirus protection against a number of arenavirus types and strains. Diagnostic and therapeutic antibodies including neutralizing antibodies for the prevention and treatment of infection by LASV and other arenaviruses are also disclosed, as well as new tools and methods for the design, production, and use of arenavirus monoclonal antibodies, including expression in engineered bacterial- and mammalian-based systems.
1. An antigen-binding composition comprising a neutralizing human monoclonal antibody or neutralizing antigen-binding antibody fragment thereof specific to glycoprotein 1 (GP1), glycoprotein precursor (GPC), or full-length glycoprotein (GP) of Lassa virus (LASV), wherein the antibody or antibody fragment comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), the V H and V L each comprising the following complementarity determining regions: a V H CDR1 of SEQ ID NO: 98, a V H CDR2 of SEQ ID NO: 99, a V H CDR3 of SEQ ID NO: 100, a V L CDR1 of SEQ ID NO: 135, a V L CDR2 of sequence Gly Ala Ser, and a V L CDR3 of SEQ ID NO: 136.
2. The composition of claim 1 , wherein the composition comprises two or more of said antibodies or antigen-binding antibody fragments.
3. The composition of claim 1 , wherein the antibody comprises a human monoclonal antibody.
4. The composition of claim 1 , wherein the antigen-binding antibody fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 fragment.
5. An antigen-binding composition comprising a neutralizing human monoclonal antibody or neutralizing antigen-binding antibody fragment thereof specific to glycoprotein 1 (GP1), glycoprotein precursor (GPC), or full-length glycoprotein (GP) of Lassa virus (LASV), wherein the antibody or antibody fragment comprises the following heavy chain variable region (V H ) and light chain variable region (V L ): a V H of SEQ ID NO: 44 and a V L of SEQ ID NO: 60.
6. The composition of claim 5 , wherein the composition comprises two or more of said antibodies or antigen-binding antibody fragments.
7. The composition of claim 5 , wherein the antibody comprises a human monoclonal antibody.
8. The composition of claim 5 , wherein the antigen-binding antibody fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 fragment.
9. A pharmaceutical composition for treating infection by a Lassa virus or lymphocytic choriomeningitis virus comprising the antibody or antibody fragment of the composition of claim 1 and a pharmaceutically acceptable carrier.
10. A diagnostic kit for detecting infection of a subject by Lassa virus or lymphocytic choriomeningitis virus comprising at least one antibody or antibody fragment of the composition of claim 1 bound to a detectable labelling group and packaged in a container; wherein the container is selected from the group consisting of a vial, a bottle, a jar, and a flexible packaging container.
11. An antibody or antibody fragment of the composition of claim 1 bound to a detectable labelling group.
12. A method of treating or preventing infection by a Lassa virus in a subject comprising administering the antibody or antibody fragment of the composition of claim 1 to the subject.
13. A method of treating a lymphocytic choriomeningitis virus infection in a subject comprising administering the antibody or antibody fragment of the composition of claim 1 to the subject.