Compositions and methods for targeting of the surfactant protein A receptor
Provided are compositions and methods for use in prophylaxis, therapy and diagnosis of conditions which involve surfactant protein receptors (SPR) including the SPR for surfactant proteins A (SPA). Specific binding partners, including mono-clonal antibodies, for the SP-R210L and SP-R210S isoforms, and methods of using such binding partners are included. Fragments of the monoclonal antibodies, and fusion proteins that contain them are also included. Also provided are methods for prophylaxis and/or therapy for an individual in need thereof by administering to the individual an effective amount of monoclonal antibody or antigen binding fragment thereof. The monoclonal antibodies are bind with specificity to epitopes in one or both of the SP-R2100L and SP-R210S isoforms.
1. A monoclonal antibody (mAb) or fragment thereof that binds with specificity to surfactant protein A SP-R210 receptor, comprising:
(I) a variable heavy chain sequence comprising:
a) a heavy chain complementarity determining region 1 (P2H10-HCDR1) comprising the sequence GYIFSDYYMR (SEQ ID NO:3); and
b) a heavy chain complementarity determining region 2 (P2H10-HCDR2) comprising the sequence DINPKNGDTFYNQKFKGK (SEQ ID NO:4); and
c) a heavy chain complementarity determining region 3 (P2H10-HCDR3) comprising the sequence REGD (SEQ ID NO:5); and
a variable light chain sequence comprising:
d) a light chain complementarity determining region 1 (P2H10-LCDR1) comprising the sequence RSSQTILHSNGNTYLE (SEQ ID NO:6); and
e) a light chain complementarity determining region 2 (P2H10-LCDR2) comprising the sequence KVSKRFS (SEQ ID NO:7): and
f) a light chain complementarity determining region 3 (P2H10-LCDR3) comprising the sequence LQGSHVPLT (SEQ ID NO:8):
or:
(II) a variable heavy chain sequence comprising:
i) a heavy chain complementarity determining region 1 (P4G4-HCDR1) comprising the sequence GYTFTDYAMH (SEQ ID NO:9): and
ii) a heavy chain complementarity determining region 2 P4G4-HCDR2) comprising the sequence VISTYNGNTKYNQKFKD (SEQ ID NO:10: and
iii) a heavy chain complementarity determining region 3 P4G4-HCDR3) comprising the sequence ARTDYDNGDYVMDY (SEQ ID NO:11):and
a variable light chain sequence comprising:
iv) a light chain complementarity determining region 1 (P4G4-LCDR1) comprising the sequence KASQDINNYLS (SEQ ID NO:12): and
v) a light chain complementarity determining region 2 (P4G4-LCDR2) comprising the sequence RANRLVD (SEQ ID NO:13): and
vi) a light chain complementarity determining region 3 (P4G4-LCDR3) comprising the sequence LQYDEFPLT (SEQ ID NO:14).
2. The monoclonal antibody or fragment thereof of claim 1 , wherein the monoclonal antibody or fragment of (I) binds with specificity to only SP-R210S isoform of the SP-R210 receptor, and wherein the monoclonal antibody or fragment thereof of (II) binds with specificity to SP-R210S and SP-R210L isoforms of the SP-R210 receptor.
3. The monoclonal antibody or fragment thereof of claim 1 , wherein the monoclonal antibody or fragment thereof is partially or fully humanized.
4. The monoclonal antibody claim 3 comprising a human IgG constant region.
5. A method for treating a viral or bacterial infection in an individual in need thereof comprising administering to the individual an effective amount of a composition comprising a monoclonal antibody or fragment thereof of claim 1 .
6. The method of claim 5 , wherein the individual is in need for treatment for a viral influenza infection.
7. The method of claim 6 , wherein the individual has pneumonia associated with the viral influenza infection.
8. An expression vector encoding a monoclonal antibody or fragment thereof of claim 1 .
9. An in vitro cell culture, wherein cells in the cell culture express the monoclonal antibody or fragment thereof according to claim 1 .
10. A hybridoma comprising a polynucleotide sequence encoding a monoclonal antibody of claim 1 .
11. A pharmaceutical composition comprising a monoclonal antibody or fragment thereof of claim 1 .