Pan-ebola virus neutralizing human antibodies and methods of use therefor
The present disclosure is directed to human antibodies binding to and neutralizing ebolavirus and methods for use thereof. A further embodiment involves a monoclonal antibody, wherein the antibody or antibody fragment is characterized by clone-paired heavy and light chain CDR sequences. In yet another embodiment, there is provided a hybridoma or engineered cell encoding an antibody or antibody fragment. An additional embodiment comprises a vaccine formulation comprising one or more antibodies or antibody fragments characterized by clone-paired heavy and light chain CDR sequences. In still a further embodiment, there is provided a method of protecting the health of a placenta and/or fetus of a pregnant a subject infected with or at risk of infection with ebolavirus comprising delivering to said subject the antibody or antibody fragment.
1. A method of treating a subject infected with ebolavirus, or reducing the likelihood of infection of a subject at risk of contracting ebolavirus, comprising administering to said subject an antibody or antibody fragment having clone-paired heavy and light chain CDR sequences selected from heavy chain CDR1-3 of SEQ ID NOS: 91, 92 and 93, and light chain CDR1-3 of SEQ ID NOS: 154, 155, and 156; heavy chain CDR1-3 of SEQ ID NOS: 118, 119 and 120, and light chain CDR1-3 of SEQ ID NOS: 181, 182, and 183; or heavy chain CDR1-3 of SEQ ID NOS: 127, 128 and 129, and light chain CDR1-3 of SEQ ID NOS: 190, 191, and 192.
2. The method of claim 1 , wherein the antibody or antibody fragment is encoded by clone-paired light and heavy chain variable sequences selected from SEQ ID NOS: 6 and 5, SEQ ID NOS: 24 and 23, or SEQ ID NOS: 30 and 29, respectively.
3. The method of claim 1 , wherein the antibody or antibody fragment is encoded by clone-paired light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 6 and 5, SEQ ID NOS: 24 and 23, or SEQ ID NOS: 30 and 29, respectively.
4. The method of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%, or 90% identity to SEQ ID NOS: 6 and 5, SEQ ID NOS: 24 and 23, or SEQ ID NOS: 30 and 29, respectively.
5. The method of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences SEQ ID NOS: 48 and 47, SEQ ID NOS: 66 and 65, or SEQ ID NOS: 72 and 71, respectively.
6. The method of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 70%, 80% or 90% identity to SEQ ID NOS: 48 and 47, SEQ ID NOS: 66 and 65, or SEQ ID NOS: 72 and 71, respectively.
7. The method of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 48 and 47, SEQ ID NOS: 66 and 65, or SEQ ID NOS: 72 and 71, respectively.
8. The method of claim 1 , wherein the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab′)2 fragment, or Fv fragment, and/or wherein said antibody fragment further comprises a cell penetrating peptide and/or is an intrabody.
9. The method of claim 1 , wherein said antibody is an IgG, a recombinant IgG antibody, or an IgG antibody fragment comprising an Fc portion mutated to alter FcR interactions, to increase half-life or glycan modified to alter FcR interactions.
10. The method of claim 1 , wherein said antibody is a chimeric antibody or a bispecific antibody, and/or wherein said antibody further comprises a cell penetrating peptide and/or is an intrabody.
11. The method of claim 1 , wherein said subject is a pregnant female, a sexually active female, or a female undergoing fertility treatments.
12. The method of claim 1 , wherein delivering comprises antibody or antibody fragment administration, or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antibody fragment.
13. A hybridoma or engineered cell encoding an antibody or antibody fragment wherein the antibody or antibody fragment is characterized by clone-paired heavy and light chain CDR sequences selected from heavy chain CDR1-3 of SEQ ID NOs: 91, 92 and 93, and light chain CDR1-3 of SEQ ID NOs: 154, 155, and 156; heavy chain CDR1-3 of SEQ ID NOs: 118, 119 and 120, and light chain CDR1-3 of SEO ID NOs: 181, 182, and 183; or heavy chain CDR1-3 of SEQ ID NOs: 127, 128 and 129, and light chain CDR1-3 of SEQ ID NOs: 190, 191, and 192.
14. A vaccine formulation comprising one or more antibodies or antibody fragments characterized by clone-paired heavy and light chain CDR sequences selected from
heavy chain CDR1-3 of SEQ ID NOs: 91, 92 and 93, and light chain CDR1-3 of SEQ ID NOs: 154, 155, and 156;
heavy chain CDR1-3 of SEQ ID NOs: 118, 119 and 120, and light chain CDR1-3 of SEO ID NOs: 181, 182, and 183; or
heavy chain CDR1-3 of SEQ ID NOs: 127, 128 and 129, and light chain CDR1-3 of SEQ ID NOs: 190, 191, and 192;
and a pharmaceutically acceptable carrier.
15. A method of detecting an ebolavirus infection in a subject comprising:
(a) contacting a sample from said subject with an antibody or antibody fragment having clone-paired heavy and light chain CDR sequences selected from heavy chain CDR1-3 of SEQ ID NOs: 91, 92 and 93, and light chain CDR1-3 of SEQ ID NOs: 154, 155, and 156; heavy chain CDR1-3 of SEQ ID NOs: 118, 119 and 120, and light chain CDR1-3 of SEO ID NOs: 181, 182, and 183; or heavy chain CDR1-3 of SEQ ID NOs: 127, 128 and 129, and light chain CDR1-3 of SEQ ID NOs: 190, 191, and 192; and
(b) detecting ebolavirus in said sample by binding of said antibody or antibody fragment to an ebolavirus antigen in said sample.