Antibodies that bind zika virus envelope protein and uses thereof
AssigneesMassachusetts Institute of Technology, National University of Singapore
InventorsRam SASISEKHARAN, Kannan THARAKARAMAN, Kuan Rong CHAN, Satoru WATANABE, Subhash G. VASUDEVAN, Eng Eong OOI
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Abstract
Isolated monoclonal antibodies which bind to Zika virus envelope protein and related antibody-based compositions and molecules are disclosed. Also disclosed are therapeutic and diagnostic methods for using the antibodies.
Claims64
An isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising heavy and light chain CDRs, wherein
- (i) heavy chain CDR1 comprises GFX1FSTY, wherein X1 may or may not be present, and if present is a polar amino acid residue;
- (ii) heavy chain CDR2 comprises X2GEGDS, wherein X2 is a polar amino acid residue;
- (iii) heavy chain CDR3 comprises GYX3NFYYYYTMDX4, wherein X3 is a polar amino acid residue and X4 is a nonpolar amino acid residue;
- (iv) light chain CDR1 comprises RAX5QSIX6TFLA, wherein X5 is a polar amino acid residue and X6 is a polar amino acid residue or a hydrophobic amino acid residue;
- (v) light chain CDR2 comprises DASTX7AX8, wherein X7 and X8 are polar amino acids;
- and
- (vi) light chain CDR3 comprises QQRYNWPPYX9, wherein X9 is a polar amino acid.
An isolated monoclonal antibody which specifically binds Zika virus envelope protein, or antigen binding portion thereof, comprising a heavy chain variable region as set forth in SEQ ID NO:
- 4, wherein
- (i) heavy chain CDR1 comprises an amino acid substitution or deletion at N28, and amino acid substitutions at L29, S31, S32;
- (ii) heavy chain CDR2 comprises amino acid substitutions at S52, S52A, S53, Y54, G55;
- (iii) heavy chain CDR3 comprises an amino acid deletion at S99 and amino acid substitutions at K100, K100A, P100B, Y100C, F100D, S100E, G100F, W100G, A100H, and Y102;
- and
- wherein the heavy chain variable region comprises at least one amino acid deletion at R94, and at CDR3 residues T95, V96, and R97, and combinations thereof, numbering according to Chothia.
An isolated monoclonal antibody, or antigen binding portion thereof, which binds to Zika virus envelope protein and comprises heavy and light chain variable regions, wherein the heavy and light chain amino acid sequences are selected from the group consisting of:
- (a) SEQ ID NOs:
- 4 and 14, respectively;
- (b) SEQ ID NOs:
- 4 and 15, respectively;
- (c) SEQ ID NOs:
- 9 and 16, respectively;
- (d) SEQ ID NOs:
- 4 and 16, respectively;
- (e) SEQ ID NOs:
- 4 and 17, respectively;
- (f) SEQ ID NOs:
- 8 and 14, respectively;
- (g) SEQ ID NOs:
- 7 and 17, respectively;
- (h) SEQ ID NOs:
- 6 and 15, respectively;
- (i) SEQ ID NOs:
- 6 and 5, respectively;
- (j) SEQ ID NOs:
- 7 and 5, respectively;
- (k) SEQ ID NOs:
- 8 and 5, respectively;
- (l) SEQ ID NOs:
- 9 and 5, respectively;
- (m) SEQ ID NOs:
- 10 and 5, respectively;
- (n) SEQ ID NOs:
- 11 and 5, respectively;
- (o) SEQ ID NOs:
- 6 and 14, respectively;
- (p) SEQ ID NOs:
- 6 and 16, respectively;
- (q) SEQ ID NOs:
- 6 and 17, respectively;
- (r) SEQ ID NOs:
- 7 and 14, respectively;
- (s) SEQ ID NOs:
- 7 and 15, respectively;
- (t) SEQ ID NOs:
- 7 and 16, respectively;
- (u) SEQ ID NOs:
- 8 and 15, respectively;
- (v) SEQ ID NOs:
- 8 and 16, respectively;
- (w) SEQ ID NOs:
- 8 and 17, respectively;
- (x) SEQ ID NOs:
- 9 and 14, respectively;
- (y) SEQ ID NOs:
- 9 and 15, respectively;
- (z) SEQ ID NOs:
- 9 and 17, respectively;
- (aa) SEQ ID NOs:
- 10 and 14, respectively;
- (bb) SEQ ID NOs:
- 10 and 15, respectively;
- (cc) SEQ ID NOs:
- 10 and 16, respectively;
- (dd) SEQ ID NOs:
- 10 and 17, respectively;
- (ee) SEQ ID NOs:
- 11 and 14, respectively;
- (ff) SEQ ID NOs:
- 11 and 15, respectively;
- (gg) SEQ ID NOs:
- 11 and 16, respectively;
- and
- (hh) SEQ ID NOs:
- 11 and 17, respectively.
An isolated monoclonal antibody, or antigen binding portion thereof, which binds to Zika virus envelope protein, comprising heavy and light chain CDRs selected from the group consisting of:
- (a) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 20, 26 and 31, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 38, 44 and 50, respectively;
- (b) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 22, 28 and 33, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 39, 45 and 51, respectively;
- (c) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 20, 26 and 31, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 39, 45 and 51, respectively;
- (d) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 20, 26 and 31, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 40, 46 and 50, respectively;
- (e) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 38, 44 and 50, respectively;
- (f) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 27 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 40, 46 and 50, respectively;
- (g) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 27 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 38, 44 and 50, respectively;
- (h) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 27 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 37, 43 and 49, respectively;
- (i) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 37, 43 and 49, respectively;
- (j) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 22, 28 and 33, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 37, 43 and 49, respectively;
- (k) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 23, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 37, 43 and 49, respectively;
- (l) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 37, 43 and 49, respectively;
- (m) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 27 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 39, 45 and 51, respectively;
- (n) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 39, 45 and 51, respectively;
- (o) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 40, 46 and 50, respectively;
- (p) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 22, 28 and 33, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 38, 44 and 50, respectively;
- (q) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 22, 28 and 33, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 40, 46 and 50, respectively;
- (r) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 23, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 38, 44 and 50, respectively;
- (s) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 23, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 39, 45 and 51, respectively;
- (t) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 23, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 40, 46 and 50, respectively;
- (u) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 38, 44 and 50, respectively;
- (v) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 39, 45 and 51, respectively;
- and
- (w) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 21, 28 and 34, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs:
- 40, 46 and 50, respectively.
An isolated monoclonal antibody, or antigen binding portion thereof, which binds to Zika virus envelope protein and comprises heavy and light chain variable regions, wherein the heavy chain variable region comprises an amino acid sequence which is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs:
- 4, 6, 7, 8, 9, 10 and 11;
- and wherein the light chain variable region comprises an amino acid sequence which is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs:
- 5, 14, 15, 16, and 17, provided that the monoclonal antibody does not comprise SEQ ID NOs:
- 4 and 5.
The isolated monoclonal antibody, or antigen binding portion thereof, according to any one of the preceding claims, having neutralizing activity against Zika virus.
The isolated monoclonal antibody, or antigen binding portion thereof, according to any one of the preceding claims, wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgD, and an IgE antibody.
A pharmaceutical composition comprising an isolated monoclonal antibody or antigen binding portion thereof, of any one of the preceding claims, and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.