Antibodies against and methods for producing vaccines for respiratory syncytial virus
The present invention relates to novel respiratory syncytial virus (RSV) F peptides and compositions comprising them. The present invention also relates to methods of evaluating anti-RSV antibody binding to F peptides. The present invention also relates to antibodies that immunospecifically bind to an F peptide of the present invention. The invention further provides methods and protocols for the administration of F peptides and/or antibodies that immunospecifically bind to F peptides for the prevention, neutralization, treatment of RSV infection. Additionally, the methods of the invention may be useful for the treatment, prevention and the amelioration of symptoms associated with RSV infection.
1. A respiratory syncytial virus (RSV) F peptide comprising an amino acid sequence at least 90% identical to the amino acid sequence of LSLINDMPITNDQKILMSS (SEQ ID NO:40) and wherein said peptide comprises an N, I, or Q at amino acid position 15 of SEQ ID NO:40 and/or an L at amino acid position 11 of SEQ ID NO:40.
2. The RSV F peptide of claim 1 , wherein said peptide is conjugated to BSA or IgG or PEG.
3. The RSV F peptide of claim 1 , wherein said peptide is labeled.
4. A pharmaceutical composition comprising the RSV F peptide of claim 1 .
5. A method of preventing an RSV infection in an animal comprising administering to said animal a prophylactically effective amount of the composition of claim 4 .
6. A method of eliciting an immune response in an animal in need thereof, comprising administering to said animal an effective amount of a composition comprising the RSV F peptide of claim 1 .
7. A method for screening anti-RSV antibodies comprising:
bringing the RSV F peptide of claim 1 into contact with an antibody or fragment thereof; and
detecting whether the antibody specifically binds the RSV F peptide.
8. The method of claim 7 , wherein the recovered anti-RSV antibodies are not palivizumab, motavizumab, murine mAbs 47F and 7C2 or anti-RSV antibodies AFFF, P12f2, P12f4, P11d4, Ale9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S;
are not an antibody comprising a VH chain and/or VL chain having the amino acid sequence of a VH chain and/or VL chain of AFFF, P12f2, P12f4, P11d4, Ale9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S; or
are not an antibody comprising one or more CDRs having the amino acid sequence of one or more CDRs of AFFF, P12f2, P12f4, P11d4, Ale9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S.
9. The method of claim 7 , wherein the anti-RSV antibody is selected from the group consisting of: a) a chimeric antibody; b) a humanized antibody; c) a human antibody; d) a single chain antibody; e) an Fab fragment; f) an F(ab′)2 fragment; g) a single chain FvFc antibody; and h) an scFv-scFv-Fc antibody.
10. A method for screening molecules that specifically bind the RSV F peptide of claim 1 , the method comprising:
bringing the isolated RSV peptide of claim 1 into contact with the molecules; and
detecting whether the molecules specifically bind the RSV F peptide.
11. The method of claim 10 , wherein said molecules are aptamers.
12. The RSV F peptide of claim 1 , wherein said peptide comprises NSELLSLINDMPITLDQKILMSS (SEQ ID NO: 35), NSELLSLINDMPITNDQKNLMSS (SEQ ID NO: 36), NSELLSLINDMPITNDQKILMSS (SEQ ID NO: 37), or NSELLSLINDMPITNDQKQLMSS (SEQ ID NO: 38).
13. The RSV F peptide of claim 1 , wherein said peptide consists of NSELLSLINDMPITLDQKILMSS (SEQ ID NO: 35), NSELLSLINDMPITNDQKNLMSS (SEQ ID NO: 36), NSELLSLINDMPITNDQKILMSS (SEQ ID NO: 37), NSELLSLINDMPITNDQKQLMSS (SEQ ID NO: 38), LSLINDMPITLDQKILMSS (SEQ ID NO: 39), or LSLINDMPITNDQKILMSS (SEQ ID NO:40).
14. The method of claim 7 , wherein the anti-RSV antibodies are produced from a population of antibody producing clones, and further comprising recovering a clone expressing the antibody or fragment thereof which specifically binds to the isolated RSV F peptide.
15. The pharmaceutical composition of claim 4 comprising a sustained release formulation.
16. The pharmaceutical composition of claim 4 formulated for intranasal or pulmonary administration.
17. The method of claim 5 comprising parenteral, epidural, or mucosal administration.
18. The method of claim 5 comprising pulmonary administration.
19. The method of claim 5 comprising intranasal administration.