Anti-malarial antibodies that bind circumsporozoite protein
Antibodies that bind to the circumsporozoite protein (CSP) of Plasmodium falciparum . Use of such antibodies as anti-malarial agents, to confer protection against infection by malarial parasites such as P. falciparum by insect vector transmission. Diagnosis of malaria using anti-CSP antibodies. Methods of determining efficacy of candidate vaccine compositions in development and testing of anti-malarial vaccines.
1. An isolated antibody that specifically binds the circumsporozoite protein (CSP) of Plasmodium falciparum , comprising the heavy and light chain complementarity determining regions of antibody 666 (SEQ ID Nos: 3-5 and 8-10, respectively), antibody 667 (SEQ ID Nos: 13-15 and 18-20, respectively), antibody 668 (SEQ ID Nos: 23-25 and 28-30, respectively) or antibody 669 (SEQ ID Nos: 33-35 and 38-40, respectively).
2. The antibody according to claim 1 , wherein the antibody is an IgG.
3. The antibody according to claim 2 , wherein the antibody is a human IgG1.
4. The antibody according to claim 2 , wherein the IgG comprises a CH2 domain having “YTE” mutations to extend the in vivo half-life of the antibody, the YTE mutations being tyrosine at residue 252, threonine at residue 254 and glutamic acid at residue 256, numbered according to the EU index of Kabat.
5. A composition comprising an isolated antibody according to claim 1 and a pharmaceutically acceptable excipient.
6. The antibody according to claim 1 , comprising the heavy and light chain complementarity determining regions of antibody 666 (SEQ ID Nos: 3-5 and 8-10, respectively).
7. The antibody according to claim 1 , comprising the heavy and light chain complementarity determining regions of antibody 667 (SEQ ID Nos: 13-15 and 18-20, respectively).
8. The antibody according to claim 1 , comprising the heavy and light chain complementarity determining regions of antibody 668 (SEQ ID Nos: 23-25 and 28-30, respectively).
9. The antibody according to claim 1 , comprising the heavy and light chain complementarity determining regions of antibody 669 (SEQ ID Nos: 33-35 and 38-40, respectively).
10. An isolated antibody comprising the VH domain of antibody 666 (SEQ ID NO: 2), and the VL domain of antibody 666 (SEQ ID NO: 7).
11. An isolated antibody comprising the VH domain of antibody 667 (SEQ ID NO: 12), and the VL domain of antibody 667 (SEQ ID NO: 17).
12. An isolated antibody comprising the VH domain of antibody 668 (SEQ ID NO: 22), and the VL domain of antibody 668 (SEQ ID NO: 27).
13. An isolated antibody comprising the VH domain of antibody 669 (SEQ ID NO: 32), and the VL domain of antibody 669 (SEQ ID NO: 37).