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1. (WO2018144425) GENERATION OF HUMAN ALLERGEN-AND HELMINTH-SPECIFIC IGE MONOCLONAL ANTIBODIES FOR DIAGNOSTIC AND THERAPEUTIC USE
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WHAT IS CLAIMED IS:

1. A method of detecting a IgE antibody with binding affinity/specificity for a dust mite antigen in a subject comprising:

(a) providing a test antibody or fragment thereof having (i) heavy chain CDR1 SEQ ID NO: 123, heavy chain CDR2 SEQ ID NO: 124, heavy chain CDR3 SEQ ID NO: 125, light chain CDR1 SEQ ID NO: 201, light chain CDR2 SEQ ID NO: 202 and light chain CDR3 SEQ ID NO: 203, or (ii) heavy chain CDR1 SEQ ID NO: 126, heavy chain CDR2 SEQ ID NO: 127, heavy chain CDR3 SEQ ID NO: 128, light chain CDR1 SEQ ID NO: 204, light chain CDR2 SEQ ID NO: 205 and light chain CDR3 SEQ ID NO: 206, or (iii) heavy chain CDR1 SEQ ID NO: 174, heavy chain CDR2 SEQ ID NO: 175, heavy chain CDR3 SEQ ID NO: 176, light chain CDR1 SEQ ID NO: 249, light chain CDR2 SEQ ID NO: 250 and light chain CDR3 SEQ ID NO: 251 ;

(b) contacting the test antibody or fragment thereof with an antibody-containing sample from said subject in the presence of a dust mite antigen; and

(c) detecting IgE antibody with binding affinity for dust mite antigen in said sample by measuring the reduction of binding to dust mite antigen by the test antibody or fragment thereof as compared to the binding of the test antibody or fragment thereof in the absence of said sample.

2. The method of claim 1, wherein said sample is a body fluid.

3. The method of claims 1-2, wherein said sample is blood, sputum, tears, saliva, mucous or serum, urine, exudate, transudate, tissue scrapings or feces.

4. The method of claims 1-3, wherein detection comprises ELISA, RIA or Western blot, and/or said detection may be quantitative.

5. The method of claims 1-4, further comprising performing steps (a) and (b) a second time and determining a change in antibody levels as compared to the first assay.

6. The method of claims 1-5, wherein the test antibody or fragment thereof is encoded by heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

7. The method of claims 1-5, wherein said test antibody or fragment thereof is encoded by heavy and light chain variable sequences having 70%, 80%>, or 90% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

8. The method of claims 1-5, wherein said test antibody or fragment thereof is encoded by heavy and light chain variable sequences having 95% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

9. The method of claims 1-5, wherein said test antibody or fragment thereof comprises heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 65 and 66, or (ii) SEQ ID NOS: 67 and 68, or (iii) SEQ ID NOS: 99 and 100.

10. The method of claims 1-5, wherein said test antibody or fragment thereof comprises heavy and light chain variable sequences having 70%, 80%> or 90% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 65 and 66, or (ii) SEQ ID NOS: 67 and 68, or (iii) SEQ ID NOS: 99 and 100.

1 1. The method of claims 1-5, wherein said test antibody or fragment thereof comprises heavy and light chain variable sequences having 95% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 65 and 66, or (ii) SEQ ID NOS: 67 and 68, or (iii) SEQ ID NOS: 99 and 100.

12. The method of claims 1-1 1, wherein the test antibody or fragment thereof is an IgE antibody or IgG antibody, and the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment.

13. A method of detecting a IgE antibody with binding affinity/specificity for a helminth antigen in a subject comprising:

(a) providing a test antibody or fragment thereof having clone paired heavy and light chain CDRs from Tables C and D;

(b) contacting the test antibody or fragment thereof with an antibody-containing sample from said subject in the presence of a helminth antigen; and

(c) detecting IgE antibody with binding affinity for helminth antigen in said sample by measuring the reduction of binding to helminth antigen by the test antibody or fragment thereof as compared to the binding of the test antibody or fragment thereof in the absence of said sample.

14. The method of claim 13, wherein said sample is a body fluid.

15. The method of claims 13-14, wherein said sample is blood, sputum, tears, saliva, mucous or serum, urine, exudate, transudate, tissue scrapings or feces.

16. The method of claims 13-15, wherein detection comprises ELISA, RIA or Western blot, and/or said detection may be quantitative.

17. The method of claims 13-16, further comprising performing steps (a) and (b) a second time and determining a change in antibody levels as compared to the first assay.

18. The method of claims 13-17, wherein the test antibody or fragment thereof is encoded by clone paired heavy and light chain variable sequences as set forth in Table A.

19. The method of claims 13-17, wherein said test antibody or fragment thereof is encoded by heavy and light chain variable sequences having 70%, 80%>, or 90% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

20. The method of claims 13-17, wherein said test antibody or fragment thereof is encoded by heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

21. The method of claims 13-17, wherein said test antibody or fragment thereof comprises clone paired heavy and light chain variable sequences as set forth in Table B.

22. The method of claims 13-17, wherein said test antibody or fragment thereof comprises heavy and light chain variable sequences having 70%, 80% or 90% identity to clone paired heavy and light chain variable sequences as set forth in Table B.

23. The method of claims 13-17, wherein said test antibody or fragment thereof comprises heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table B.

24. The method of claims 13-23, wherein the test antibody or fragment thereof is an IgE antibody or IgG antibody, and the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment.

25. A method of detecting an allergen or antigen in a sample comprising:

(a) providing a test antibody or fragment thereof having heavy chain CDR1-CDR3 and light chain CDR4-CDR6 from an IgE antibody produced in a subject in response to allergen or antigen stimulation;

(b) contacting the test antibody or fragment thereof with a sample suspect of containing an allergen or antigen; and

(c) detecting allergen or antigen in said sample by binding of the test antibody or fragment.

26. The method of claim 25, wherein said sample is an environmental sample.

27. The method of claims 25-26, wherein said sample is a food stuff.

28. The method of claims 25-27, wherein detection comprises ELISA, RIA or Western blot.

29. The method of claims 25-28, wherein detection of said allergen or antigen is quantitative.

30. The method of claims 25-29, wherein the allergen is peanut allergen and the test antibody or fragment thereof has (i) heavy chain CDRl SEQ ID NO: 105, heavy chain CDR2 SEQ ID NO: 106, heavy chain CDR3 SEQ ID NO: 107, light chain CDRl SEQ ID NO: 183, light chain CDR2 SEQ ID NO: 184 and light chain CDR3 SEQ ID NO: 185, or (ii) heavy chain CDRl SEQ ID NO: 106, heavy chain CDR2 SEQ ID NO: 107, heavy chain CDR3 SEQ ID NO: 108, light chain CDRl SEQ ID NO: 186, light chain CDR2 SEQ ID NO: 187 and light chain CDR3 SEQ ID NO: 188, or (iii) heavy chain CDRl SEQ ID NO: 165, heavy chain CDR2 SEQ ID NO: 166, heavy chain CDR3 SEQ ID NO: 167, light chain CDRl SEQ ID NO: 240, light chain CDR2 SEQ ID NO: 241 and light chain CDR3 SEQ ID NO: 242, or (iv) heavy chain CDRl SEQ ID NO: 168, heavy chain CDR2 SEQ ID NO: 169, heavy chain CDR3 SEQ ID NO: 170, light chain CDRl SEQ ID NO: 243, light chain CDR2 SEQ ID NO: 244 and light chain CDR3 SEQ ID NO: 245, or (v) heavy chain CDRl SEQ ID NO: 171, heavy chain CDR2 SEQ ID NO: 172, heavy chain CDR3 SEQ ID NO: 173, light chain CDRl SEQ ID NO: 246, light chain CDR2 SEQ ID NO: 247 and light chain CDR3 SEQ ID NO: 248.

31. The method of claims 25-29, wherein the allergen is a dust mite allergen and the test antibody or fragment thereof has (i) heavy chain CDRl SEQ ID NO: 105, heavy chain CDR2 SEQ ID NO: 106, heavy chain CDR3 SEQ ID NO: 107, light chain CDRl SEQ ID NO: 183, light chain CDR2 SEQ ID NO: 184 and light chain CDR3 SEQ ID NO: 185, or

(ii) heavy chain CDR1 SEQ ID NO: 106, heavy chain CDR2 SEQ ID NO: 107, heavy chain CDR3 SEQ ID NO: 108, light chain CDR1 SEQ ID NO: 186, light chain CDR2 SEQ ID NO: 187 and light chain CDR3 SEQ ID NO: 188, or (iii) heavy chain CDR1 SEQ ID NO: 165, heavy chain CDR2 SEQ ID NO: 166, heavy chain CDR3 SEQ ID NO: 167, light chain CDR1 SEQ ID NO: 240, light chain CDR2 SEQ ID NO: 241 and light chain CDR3 SEQ ID NO: 242, or (iv) heavy chain CDR1 SEQ ID NO: 168, heavy chain CDR2 SEQ ID NO: 169, heavy chain CDR3 SEQ ID NO: 170, light chain CDR1 SEQ ID NO: 243, light chain CDR2 SEQ ID NO: 244 and light chain CDR3 SEQ ID NO: 245, or (v) heavy chain CDR1 SEQ ID NO: 171, heavy chain CDR2 SEQ ID NO: 172, heavy chain CDR3 SEQ ID NO: 173, light chain CDR1 SEQ ID NO: 246, light chain CDR2 SEQ ID NO: 247 and light chain CDR3 SEQ ID NO: 248.

32. The method of claims 25-29, wherein the antigen is a helminth antigen and the test antibody or fragment thereof has clone paired heavy and light chain CDRs from Tables C and D.

33. The method of claims 30, wherein said test antibody or fragment thereof comprises clone paired heavy and light chain variable sequences as set forth in Table B, or heavy and light chain variable sequences having 70%, 80% or 90% of clone paired heavy and light chain variable sequences of Table B.

34. The method of claims 31, wherein said test antibody or fragment thereof comprises clone paired heavy and light chain variable sequences as set forth in Table B, or heavy and light chain variable sequences having 70%, 80% or 90% of clone paired heavy and light chain variable sequences of Table B.

35. The method of claims 32, wherein said test antibody or fragment thereof comprises clone paired heavy and light chain variable sequences as set forth in Table B, or heavy and light chain variable sequences having 70%, 80% or 90% of clone paired heavy and light chain variable sequences of Table B.

36. The method of claims 25-35, wherein the test antibody or fragment thereof is an IgE antibody or IgG antibody, and the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment.

37. A method of preventing or treating a dust mite-related allergic reaction in a subject comprising delivering to said subject an IgG antibody or antibody fragment, wherein said antibody or antibody fragment has (i) heavy chain CDR1 SEQ ID NO: 123, heavy chain CDR2 SEQ ID NO: 124, heavy chain CDR3 SEQ ID NO: 125, light chain CDR1 SEQ ID NO: 201, light chain CDR2 SEQ ID NO: 202 and light chain CDR3 SEQ ID NO: 203, or (ii) heavy chain CDR1 SEQ ID NO: 126, heavy chain CDR2 SEQ ID NO: 127, heavy chain CDR3 SEQ ID NO: 128, light chain CDR1 SEQ ID NO: 204, light chain CDR2 SEQ ID NO: 205 and light chain CDR3 SEQ ID NO: 206, or (iii) heavy chain CDR1 SEQ ID NO: 174, heavy chain CDR2 SEQ ID NO: 175, heavy chain CDR3 SEQ ID NO: 176, light chain CDR1 SEQ ID NO: 249, light chain CDR2 SEQ ID NO: 250 and light chain CDR3 SEQ ID NO: 251.

38. The method of claims 37, wherein the antibody or antibody fragment is encoded by heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

39. The method of claims 37-38, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 70%, 80%, or 90% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

40. The method of claims 37-39, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 95% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

41. The method of claims 37-39, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

42. The method of claims 37-39, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 70%, 80% or 90% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

43. The method of claims 37-39, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 95% identity to heavy and light chain variable sequences as set forth in (i) SEQ ID NOS: 13 and 14, or (ii) SEQ ID NOS: 15 and 16, or (iii) SEQ ID NOS: 47 and 48.

44. The method of claims 37-43, wherein said antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment, a chimeric antibody.

45. The method of claims 37-44, further comprising treating said subject with an antiinflammatory agent.

46. The method of claim 45, wherein said anti-inflammatory agent is selected from the group consisting of a steroid, an anti-histamine, and anti-leukotriene.

47. The method of claim 45, wherein said anti-inflammatory agent is administered chronically.

48. The method of claims 37-47, wherein delivering comprises antibody or antibody fragment administration.

49. The method of claims 37-47, wherein delivering comprises genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antibody fragment.

50. A monoclonal antibody or antibody fragment comprises clone paired heavy and light chain CDRs from Tables C and D.

51. The monoclonal antibody or antibody fragment of claim 50, wherein the antibody or antibody fragment is encoded by clone paired heavy and light chain variable sequences from Table A.

52. The monoclonal antibody or antibody fragment of claim 50, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 70%, 80%), or 90% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

53. The monoclonal antibody or antibody fragment of claim 50, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

54. The monoclonal antibody or antibody fragment of claim 50, wherein said antibody or antibody fragment comprises clone paired heavy and light chain variable sequences as set forth in Table B.

55. The monoclonal antibody or antibody fragment of claim 50, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 70%, 80%> or 90%) identity to clone paired heavy and light chain variable sequences as set forth in Table B.

56. The monoclonal antibody or antibody fragment of claim 50, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table B.

57. The monoclonal antibody of claims 50-56, wherein the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment, or is a chimeric antibody, a bispecific antibody.

58. The monoclonal antibody of claims 50-57, wherein said antibody is an IgE, or is an IgG comprising grafted IgE CDRs or variable regions.

59. The monoclonal antibody of claims 50-58, wherein said antibody or antibody fragment further comprises a cell penetrating peptide and/or is an intrabody.

60. A hybridoma or engineered cell encoding an antibody or antibody fragment wherein the antibody or antibody fragment is characterized by clone paired heavy and light chain CDRs from Tables C and D.

The hybridoma or engineered cell of claim 61, wherein the antibody or antibody fragment is encoded by clone paired heavy and light chain variable sequences as set forth in Table

62. The hybridoma or engineered cell of claim 61, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 70%, 80%, or 90% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

63. The hybridoma or engineered cell of claim 61, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

64. The hybridoma or engineered cell of claim 61, wherein said antibody or antibody fragment comprises clone paired heavy and light chain variable sequences as set forth in Table B. 65. The hybridoma or engineered cell of claim 61, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 70%, 80% or 90% identity to clone paired heavy and light chain variable sequences as set forth in Table B.

66. The hybridoma or engineered cell of claim 61, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table B.

67. The hybridoma or engineered cell of claims 61-66, wherein the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment.

68. The hybridoma or engineered cell of claim 61-67, wherein said antibody is a chimeric antibody, a bispecific antibody, is an IgE, or is an IgG.

69. The hybridoma or engineered cell of claims 61-68, wherein said antibody or antibody fragment further comprises a cell penetrating peptide and/or is an intrabody.

70. A vaccine formulation comprising one or more IgG antibodies or antibody fragments characterized by clone paired heavy and light chain CDRs from Tables C and D.

71. The vaccine formulation of claim 70, wherein the antibody or antibody fragment is encoded by clone paired heavy and light chain variable sequences as set forth in Table A.

72. The vaccine formulation of claim 70, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 70%, 80%, or 90% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

73. The vaccine formulation of claim 70, wherein said antibody or antibody fragment is encoded by heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table A.

74. The vaccine formulation of claim 70, wherein said antibody or antibody fragment comprises clone paired heavy and light chain variable sequences as set forth in Table B.

75. The vaccine formulation of claim 70, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 70%, 80% or 90% identity to clone paired heavy and light chain variable sequences as set forth in Table B.

76. The vaccine formulation of claim 70, wherein said antibody or antibody fragment comprises heavy and light chain variable sequences having 95% identity to clone paired heavy and light chain variable sequences as set forth in Table B.

77. The vaccine formulation of claims 70-76, wherein at least one of said antibody fragments is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment, or is a chimeric antibody, or is bispecific antibody.

78. The vaccine formulation of claims 70-76, wherein at least one of said antibodies or antibody fragments further comprises a cell penetrating peptide and/or is an intrabody.

79. A method of generating a hydridoma that produces an IgE antibody comprising:

(a) activating one or more peripheral blood mononuclear cells (PBMC's) with rh-IL- 21, CD40L and BAFF;

(b) screening the activated cell or cells of step (a) for IgE expression;

(c) fusing one or more IgE-expressing PMBCs identified in step (b) with an immortal cell;

(d) subjecting a fused cell or cells of step (c) to selection for a fusion event;

(e) screening one or more selected fused cells of step (d) binding to an antigen;

(f) cloning one or more selected fused cells positive for antigen binding; and

(g) propagating one or more cloned cells of step (f).

80. The method of claim 79, further comprising obtaining IgE antibody produced from the one or more cloned cells of step (g).

81. The method of claim 79, further comprising obtaining a PMBC-containing sample from a subject prior to step (a).

82. The method of claim 79, further comprising isolating one or more PMBCs from a blood sample prior to step (a).

83. The method of claim 79, wherein step (d) comprises ELISA.

84. The method of claim 79, wherein cloning comprises limiting dilution and/or flow cytometry.

85. The method of claim 79, wherein said antigen is a parastic worm antigen.

86. The method of claim 85, wherein said parasitic worm is Wuchereria bancrofli or Stronglyoides stercoralis.

87. The method of claim 85, wherein said antigen is an allergen.

88. The method of claim 87, wherein said allergen is a mold antigen, a dust mite antigen, an insect venom, an antibiotic, a food antigen, or an animal antigen.

89. A method of de-sensitizing a subject to an allergen comprising:

(a) administering to said subject an allergen; and

(b) administering to said subject an IgG antibody that has a binding specificity to said allergen obtained from an IgE antibody.

90. The method of claim 89, wherein said allergen and said IgG antibody are mixed together prior to administering.

91. The method of claim 89, wherein said allergen and said IgG antibody are administered to said subject separately.

92. The method of claim 89, wherein said allergen and said IgG antibody are administered to said subject multiple times.

93. The method of claim 89, wherein said subject is a human or a non-human mammal.

94. The method of claim 89, wherein said allergen is administered with an adjuvant.

95. A method of producing an IgG immune response to an allergen comprising:

(a) identifying an IgE epitope in an allergen by mapping the binding of an IgE antibody binding site;

(b) modifying one or more residues in said IgE antibody binding site to reduce or eliminate IgE antibody binding to said binding site, thereby producing a hypoallergenic allergen;

(c) immunizing a subject with said hypoallergenic allergen to produce and IgG resopnse to said hypoallegenic allergen, while producing a reduced or no IgE response as compared to the allergen of step (a).

96. The method claim 95, wherein said allergen is is a mold allergen, a dust mite allergen, an insect venom, an antibiotic, a food allergen, or an animal allergen.

97. The method of claim 95, wherein IgE antibody binding to said binding site is reduced by at least 90%.

98. The method of claim 95, wherein IgE antibody binding to said binding site is eliminated.

99. The method of claim 95, wherein said hypoallergenic allergen is administered to said subject with an adjuvant and/or is administered multiple times.

100. A method of identifying an IgE antigen comprising:

(a) obtaining an IgE-producing B cell;

(b) immortalizing said IgE-producing B cell;

(c) obtaining monoclonal IgE from the immortalized B cell of step (b);

(d) identifying an antigen that binds to said monoclonal IgE.

101. The method claim 100, wherein said antigen is an allergen.

102. The method of claim 101, wherein siad allergen is is a mold allergen, a dust mite allergen, an insect venom, an antibiotic, a food allergen, or an animal allergen.

103. The method of claim 101, wherein said antigen is a parastitic worm antigen.

104. The method of claim 101, further comprising producing a vaccine that lacks said IgE epitope.

105. A method of determining the antigenic integrity of an antigen comprising:

(a) contacting a sample comprising said antigen with a first antibody or antibody fragment having clone-paired heavy and light chain CDR sequences from Tables C and D, respectively; and

(b) determining antigenic integrity of said antigen by detectable binding of said antibody or antibody fragment to said antigen.

106. The method of claim 105, wherein said sample comprises recombinantly produced antigen.

107. The method of claim 105, wherein said sample comprise a vaccine formulation or

vaccine production batch.

108. The method of claims 105-107, wherein detection comprises ELISA, RIA, western blot, a biosensor using surface plasmon resonance or biolayer interferometry, or flow cytometric staining.

109. The method of claims 105-107, wherein the first antibody or antibody fragment is encoded by clone-paired variable sequences as set forth in Table A.

1 10. The method of claims 105-107, wherein said first antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%, or 90% identity to clone- paired variable sequences as set forth in Table A.

1 1 1. The method of claims 105-107, wherein said first antibody or antibody fragment is encoded by light and heavy chain variable sequences having 95% identity to clone-paired sequences as set forth in Table A.

The method of claims 105-107, wherein said first antibody or antibody fragment comprises light and heavy chain variable sequences according to clone-paired sequences from Table B.

1 13. The method of claims 105-107, wherein said first antibody or antibody fragment comprises light and heavy chain variable sequences having 70%, 80% or 90% identity to clone-paired sequences from Table B.

1 14. The method of claims 105-107, wherein said first antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to clone-paired sequences from Table B.

1 15. The method of claims 105-1 14, wherein the first antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment.

1 16. The method of claims 105-1 15, further comprising steps (a) and (b) a second time to determine the antigenic stability of the antigen over time.

1 17. The method of claims 105-116, further comprising:

(c) contacting a sample comprising said antigen with an antibody or antibody fragment having clone-paired heavy and light chain CDR sequences from Tables C and D, respectively; and

(d) determining antigenic integrity of said antigen by detectable binding of said

antibody or antibody fragment to said antigen.

1 18. The method of claim 1 17, wherein the second antibody or antibody fragment is encoded by clone-paired variable sequences as set forth in Table A.

1 19. The method of claim 1 17, wherein said second antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%>, or 90% identity to clone- paired variable sequences as set forth in Table A.

120. The method of claim 1 17, wherein said second antibody or antibody fragment is encoded by light and heavy chain variable sequences having 95% identity to clone-paired sequences as set forth in Table A.

121. The method of claims 1 17, wherein said second antibody or antibody fragment comprises light and heavy chain variable sequences according to clone-paired sequences from Table B.

122. The method of claim 1 17, wherein said second antibody or antibody fragment comprises light and heavy chain variable sequences having 70%, 80% or 90% identity to clone-paired sequences from Table B.

123. The method of claim 1 17, wherein said second antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to clone-paired sequences from Table B.

124. The method of claim 1 17-123, wherein the second antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment.

125. The method of claims 1 17-124, further comprising steps (c) and (d) a second time to determine the antigenic stability of the antigen over time.