Search

US-12624091-B2 - HIV/HCV cross-reactive antibodies and uses thereof

US12624091B2US 12624091 B2US12624091 B2US 12624091B2US-12624091-B2

Abstract

The present disclosure relates to antibodies and uses thereof for treating an HIV infection, an HCV infection, or an HIV/HCV co-infection.

Inventors

  • Kelsey PILEWSKI
  • Ivelin Stefanov Georgiev

Assignees

  • VANDERBILT UNIVERSITY

Dates

Publication Date
20260512
Application Date
20200403

Claims (19)

  1. 1 . A recombinant antibody for binding both Human Immunodeficiency virus (HIV) and Hepatitis C virus (HCV), said antibody comprising a light chain variable region (VL) that comprises a light chain complementarity determining region (CDRL) 1, CDRL2, and CDRL3 and a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region (CDRH) 1, CDRH2, and CDRH3, wherein: (i) CDRH1 is SEQ ID NO: 13107, CDRH2 is SEQ ID NO: 13113, CDRH3 is SEQ ID NO: 110 or 1822, CDRL1 is SEQ ID NO: 13125, CDRL2 is SEQ ID NO: 13131, and CDRL3 is SEQ ID NO: 101 or 1888; (ii) CDRH1 is SEQ ID NO: 13106, CDRH2 is SEQ ID NO: 13112, CDRH3 is SEQ ID NO: 104 or 1821, CDRL1 is SEQ ID NO: 13124, CDRL2 is SEQ ID NO: 13130, and CDRL3 is SEQ ID NO: 88 or 1887; (iii) CDRH1 is SEQ ID NO: 13102, CDRH2 is SEQ ID NO: 13108, CDRH3 is SEQ ID NO: 1817, CDRL1 is SEQ ID NO: 13120, CDRL2 is SEQ ID NO: 13126, and CDRL3 is SEQ ID NO: 13 or 1883; (iv) CDRH1 is SEQ ID NO: 13103, CDRH2 is SEQ ID NO: 13109, CDRH3 is SEQ ID NO: 1818, CDRL1 is SEQ ID NO: 13121, CDRL2 is SEQ ID NO: 13127, and CDRL3 is SEQ ID NO: 25 or 1884; (v) CDRH1 is SEQ ID NO: 13104, CDRH2 is SEQ ID NO: 13110, CDRH3 is SEQ ID NO: 1819, CDRL1 is SEQ ID NO: 13122, CDRL2 is SEQ ID NO: 13128, and CDRL3 is SEQ ID NO: 39 or 1885; or (vi) CDRH1 is SEQ ID NO: 13105, CDRH2 is SEQ ID NO: 13111, CDRH3 is SEQ ID NO: 1820, CDRL1 is SEQ ID NO: 13123, CDRL2 is SEQ ID NO: 13129, and CDRL3 is SEQ ID NO: 49 or 1886.
  2. 2 . The recombinant antibody of claim 1 , wherein the VL comprises an amino acid sequence selected from SEQ ID NOs: 119, 227, 242, 351, 1399, 1406, and 1899-1904.
  3. 3 . The recombinant antibody of claim 1 , wherein the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1694-1756.
  4. 4 . The recombinant antibody of claim 1 , wherein the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1895-1898, 1694, and 1718.
  5. 5 . A method of treating a HIV/HCV co-infection comprising administering to a subject a therapeutically effective amount of the recombinant antibody of claim 1 .
  6. 6 . A method of treating an HIV infection comprising administering to a subject a therapeutically effective amount of the recombinant antibody of claim 1 .
  7. 7 . A method of treating an HCV infection comprising administering to a subject a therapeutically effective amount of the recombinant antibody of claim 1 .
  8. 8 . The recombinant antibody of claim 1 , wherein CDRH1 is SEQ ID NO: 13107, CDRH2 is SEQ ID NO: 13113, CDRH3 is SEQ ID NO: 110 or 1822, CDRL1 is SEQ ID NO: 13125, CDRL2 is SEQ ID NO: 13131, and CDRL3 is SEQ ID NO: 101 or 1888.
  9. 9 . The recombinant antibody of claim 8 , wherein the VH comprises SEQ ID NO: 1718, or an amino acid sequence at least 60% identical thereto, and wherein the VL comprises SEQ ID NO: 1406, or an amino acid sequence at least 60% identical thereto.
  10. 10 . The recombinant antibody of claim 1 , wherein CDRH1 is SEQ ID NO: 13106, CDRH2 is SEQ ID NO: 13112, CDRH3 is SEQ ID NO: 104 or 1821, CDRL1 is SEQ ID NO: 13124, CDRL2 is SEQ ID NO: 13130, and CDRL3 is SEQ ID NO: 88 or 1887.
  11. 11 . The recombinant antibody of claim 10 , wherein the VH comprises SEQ ID NO: 1694, or an amino acid sequence at least 60% identical thereto, and wherein the VL comprises SEQ ID NO: 1399 or 1903, or an amino acid sequence at least 60% identical thereto.
  12. 12 . The recombinant antibody of claim 1 , wherein CDRH1 is SEQ ID NO: 13102, CDRH2 is SEQ ID NO: 13108, CDRH3 is SEQ ID NO: 1817, CDRL1 is SEQ ID NO: 13120, CDRL2 is SEQ ID NO: 13126, and CDRL3 is SEQ ID NO: 13 or 1883.
  13. 13 . The recombinant antibody of claim 12 , wherein the VH comprises SEQ ID NO: 1895, or an amino acid sequence at least 60% identical thereto, and wherein the VL comprises SEQ ID NO: 1899, or an amino acid sequence at least 60% identical thereto.
  14. 14 . The recombinant antibody of claim 1 , wherein CDRH1 is SEQ ID NO: 13103, CDRH2 is SEQ ID NO: 13109, CDRH3 is SEQ ID NO: 1818, CDRL1 is SEQ ID NO: 13121, CDRL2 is SEQ ID NO: 13127, and CDRL3 is SEQ ID NO: 25 or 1884.
  15. 15 . The recombinant antibody of claim 14 , wherein the VH comprises SEQ ID NO: 1896, or an amino acid sequence at least 60% identical thereto, and wherein the VL comprises SEQ ID NO: 1900, or an amino acid sequence at least 60% identical thereto.
  16. 16 . The recombinant antibody of claim 1 , wherein CDRH1 is SEQ ID NO: 13104, CDRH2 is SEQ ID NO: 13110, CDRH3 is SEQ ID NO: 1819, CDRL1 is SEQ ID NO: 13122, CDRL2 is SEQ ID NO: 13128, and CDRL3 is SEQ ID NO: 39 or 1885.
  17. 17 . The recombinant antibody of claim 16 , wherein the VH comprises SEQ ID NO: 1897, or an amino acid sequence at least 60% identical thereto, and wherein the VL comprises SEQ ID NO: 1901, or an amino acid sequence at least 60% identical thereto.
  18. 18 . The recombinant antibody of claim 1 , wherein CDRH1 is SEQ ID NO: 13105, CDRH2 is SEQ ID NO: 13111, CDRH3 is SEQ ID NO: 1820, CDRL1 is SEQ ID NO: 13123, CDRL2 is SEQ ID NO: 13129, and CDRL3 is SEQ ID NO: 49 or 1886.
  19. 19 . The recombinant antibody of claim 18 , wherein the VH comprises SEQ ID NO: 1898, or an amino acid sequence at least 60% identical thereto, and wherein the VL comprises SEQ ID NO: 1902, or an amino acid sequence at least 60% identical thereto.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a United States National Phase Patent Application of International Patent Application Number PCT/US2020/026552, filed on Apr. 3, 2020, which claims the benefit of U.S. Provisional Patent Application Ser. No. 62/829,526 filed Apr. 4, 2019 and U.S. Provisional Patent Application Ser. No. 62/971,477 filed Feb. 7, 2020, the disclosures of which are expressly incorporated herein by reference. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH This invention was made with government support under Grant Nos. AI131722 and AI152693, awarded by the National Institutes of Health. The government has certain rights in the invention. REFERENCE TO SEQUENCE LISTING The Sequence Listing submitted Apr. 3, 2020, as a text file named “10644-095WO1_2020_04_03_ST25.txt,” created on Apr. 3, 2020, and having a size of 4 MB is hereby incorporated by reference pursuant to 37 C.F.R. § 1.52 (e)(5). FIELD The present disclosure relates to antibodies and uses thereof for treating an HIV infection, an HCV infection, or an HIV/HCV co-infection. BACKGROUND HIV and HCV on their own are associated with devastating pathologies, affecting up to 200 million people combined. The prevalence of co-infection with these two pathogens is also high, estimated at 4-5 million people worldwide. While the global health burden of these viruses has been lessened significantly by the advent of highly active antiretroviral therapy (HAART) and direct-acting antivirals (DAA) for HIV and HCV respectively, these therapies are expensive and require high patient compliance to often complex drug regimens. Furthermore, re-infection rates are high, especially for HIV/HCV co-infected individuals, which have been reported as having the highest risk of re-infection with either virus, with re-infection rates >20%. Therefore, even though effective drug therapies for HIV and HCV already exist, a number of factors including drug resistance, patient compliance, and likelihood of re-infection, strongly motivate work toward developing alternative therapeutic and prophylactic tools. Such new tools will be of great utility in the setting of HIV/HCV co-infection, where the chronic exposure to two constantly evolving pathogens leads to significantly exacerbated health problems compared to mono-infection with either pathogen. What is needed are novel compositions and methods for treating HIV and HCV mono-infections and HIV/HCV co-infection. SUMMARY Disclosed herein are recombinant antibodies and uses thereof for preventing, treating, inhibiting, or reducing HIV and/or HCV infection. In some aspects, disclosed herein is a recombinant antibody, said antibody comprising a light chain variable region (VL) that comprises a light chain complementarity determining region (CDRL) 1, CDRL2, and CDRL3 and a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region (CDRH) 1, CDRH2, and CDRH3, wherein: CDRL3 comprises an amino acid sequence at least 60% identical to (SEQ ID NO: 13)MQPLQLPDT, (SEQ ID NO: 25)QQSYNVPT, (SEQ ID NO: 39)HQSSSLPFT, (SEQ ID NO: 49)QHFYSSPPT, (SEQ ID NO: 88)CLYAGSYSWV,or (SEQ ID NO: 101)QVWDSSSEHVV; and/or CDRH3 comprises an amino acid sequence at least 60% identical to (SEQ ID NO: 104)ARVAPPGVVNNKWFDI, (SEQ ID NO: 110)ARSEKRVTMTRKIKGRWFGP, (SEQ ID NO: 1817)CAAGLWSGDLSRPRYSDSW, (SEQ ID NO: 1818)CAKGLTTESRLEFW, (SEQ ID NO: 1819)CVSSWGPESPYYFDYW,or (SEQ ID NO: 1820)CAREYCTGGDCHFFLDYW. In some embodiments, the CDRL3 comprises at least one amino acid substitution when compared to SEQ ID NO: 13, 25, 39, 49, 88, or 101. In some embodiments, the at least one amino acid substitution is selected from the group consisting of a) at position 1 when compared to SEQ ID NO: 13, wherein the substituting amino acid residue is K;b) at position 3 when compared to SEQ ID NO: 13, wherein the substituting amino acid residue is selected from the group consisting of A, T, G, V, D, Y, and F;c) at position 6 when compared to SEQ ID NO: 13, wherein the substituting amino acid residue is selected from the group consisting of H, S, T, P, I, V, P, R, and V;d) at position 9 when compared to SEQ ID NO: 13, wherein the substituting amino acid residue is selected from the group consisting of Y, L, H, P, I, G, C, J, R, and Q;e) at position 5 when compared to SEQ ID NO: 25, wherein the substituting amino acid residue is selected from the group consisting of T, P, Y, R, I, G, and S;f) at position 6 when compared to SEQ ID NO: 25, wherein the substituting amino acid residue is selected from the group consisting of A, T, and P;g) at position 7 when compared to SEQ ID NO: 25, wherein the substituting amino acid residue is selected from the group consisting of W, A, R, G and L;h) at position 3 when compared to SEQ ID NO: 39, wherein the substituting amino acid residue is T;i) at position 4 when compared to SEQ ID NO: 39, wherein the substituting amino acid residue is selected from the group consisting of R, G, T, Y,