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1. (WO2019067592) TREATMENT AND DETECTION OF INFECTION AND DISEASE ASSOCIATED WITH DIFFERENT FUNGAL PATHOGENS
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What is claimed is:

1. A method of treating or protecting a subject against infection and/or disease caused by different fungal pathogens, the method comprising: administering to a subject in need thereof a peptide immunogen derived from the Kexin protein of a Pneumocystis fungal pathogen, an isolated antiserum comprising an antibody against the peptide immunogen, or an isolated and purified antibody against the peptide immunogen in an amount effective for the subject to acquire cross-protective immunity against infection and/or disease associated with two or more of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens.

2. A method of treating a subject having a disease or dysfunction associated with infection by different fungal pathogens, the method comprising: administering to a subject in need thereof a peptide immunogen derived from the Kexin protein of a Pneumocystis fungal pathogen, an isolated antiserum comprising an antibody against the peptide immunogen, or an isolated and purified antibody against the peptide immunogen in an amount effective to treat the subject for the disease or dysfunction associated with infection by two or more of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens.

3. The method of claim 1 or claim 2, wherein the antiserum comprises a monoclonal antibody, a polyclonal antibody, or a combination thereof.

4. The method of any one of claims 1 -3, wherein the antibody is generated against a Kex peptide of Pneumocystis hominis or Pneumocystis jirovecii.

5. The method of any one of claims 1 -4, wherein the cross-protection or treatment is against infection and/or disease or dysfunction associated with one or more of Aspergillus fumigatus, Candida albicans, or Cryptococcus neoformans.

6. The method of any one of claims 1 -5, wherein the subject is cross-protected against or treated for a disease or dysfunction selected from pulmonary disease, poor pulmonary function, or a symptom thereof.

7. The method of any one of claims 1 -6, wherein the antibody is generated in the subject against the 90-amino acid Kex peptide derived from the Pneumocystis hominis or

Pneumocystis jirovecii fungal pathogen.

8. A method of treating or protecting a subject against infection and/or disease caused by different fungal pathogens, the method comprising: administering to a subject in need thereof a peptide immunogen derived from the Kexin protein of a fungal pathogen, an isolated antiserum comprising an antibody against the peptide immunogen, or an isolated and purified antibody against the peptide immunogen, wherein the fungal pathogen is selected from one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus in an amount effective for the subject to acquire cross-protective immunity against infection and/or disease associated with two or more of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens.

9. A method of treating a subject having a disease or dysfunction associated with infection by different fungal pathogens, the method comprising: administering to a subject in need thereof a peptide immunogen derived from the Kexin protein of a fungal pathogen, an isolated antiserum comprising an antibody against the peptide immunogen, or an isolated and purified antibody against the peptide immunogen, wherein the fungal pathogen is selected from one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus in an amount effective for the subject to treat a disease or dysfunction associated with infection by at least two of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens.

10. The method of claim 8 or claim 9, wherein the antiserum comprises a monoclonal antibody, a polyclonal antibody, or a combination thereof.

11. The method of any one of claims 8-10, wherein the peptide immunogen is a Kexl peptide derived from Pneumocystis hominis or Pneumocystis jirovecii.

12. The method of claim 11, wherein the Pneumocystis Kexl peptide is a 90-amino acid peptide and is encoded by a polynucleotide contained in an expression vector.

13. The method of claim 8 or claim 9, wherein the peptide immunogen is a Kexl peptide derived from Candida albicans.

14. The method of claim 13, wherein the Candida Kexl peptide is an 88-amino acid peptide and is encoded by a polynucleotide contained in an expression vector.

15. The method of any one of claims 8-10, wherein the peptide immunogen is a Kexl peptide derived from Aspergillus fumigatus.

16. The method of claim 15, wherein the Aspergillus Kexl peptide is an 88-amino acid peptide and is encoded by a polynucleotide contained in an expression vector.

17. The method any one of claims 8-10, wherein the peptide immunogen is a Kexl peptide derived from Cryptococcus neoformans.

18. The method of claim 17, wherein the Cryptococcus Kexl peptide is a 117-amino acid peptide and is encoded by a polynucleotide contained in an expression vector.

19. A method of treating or preventing an infection, the method comprising administering to a subject infected or at risk of infection by two or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens an effective amount of an isolated antiserum comprising an antibody, or an isolated and purified antibody, which is generated by an immune response to one of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens in an independent donor subject.

20. The method of claim 19, wherein the antiserum or the isolate and purified antibody comprises an antibody or an antigen-binding fragment thereof which binds a Kex peptide of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogen.

21. A method of treating or preventing an infection, the method comprising administering to a subject infected or at risk of infection by two or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens an effective amount of an isolated antiserum comprising an antibody, or an isolated and purified antibody, which is generated by an immune response to a Kex peptide of a Pneumocystis fungal pathogen in an independent donor subject.

22. A method of treating or preventing an infection, the method comprising administering to a subject infected or at risk of infection by any one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens an effective amount of an isolated antiserum comprising an antibody, or an isolated and purified antibody, which is generated by an immune response to a Kex peptide of an Aspergillus fungal pathogen in an independent donor subject.

23. A method of treating or preventing an infection, the method comprising administering to a subject infected or at risk of infection by any one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens an effective amount of an isolated antiserum comprising an antibody, or an isolated and purified antibody, which is generated by an immune response to a Kex peptide of a Candida fungal pathogen in an independent donor subject.

24. A method of treating or preventing an infection, the method comprising administering to a subject infected or at risk of infection by any one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens an effective amount of an isolated antiserum comprising an antibody, or an isolated and purified antibody, which is generated by an immune response to a Kex peptide of a Cryptococcus fungal pathogen in an independent donor subject.

25. The method of any one of claims 1-24, wherein the antibody binds the fungal pathogen so as to treat or protect the subject against disease associated with infection.

26. The method of any one of claims 1-25, wherein the subject is a mammal.

27. The method of claim 26, wherein the subject is a human.

28. The method of any one of claims 1-27, wherein the isolated and purified antibody results from exposure of a subject to infection by one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens and/or from disease associated with said infection.

29. The method of any one of claims 1-28, wherein the subject has or is at risk of having an infection or disease caused by more than one fungal pathogen selected from Pneumocystis,

Aspergillus, Candida, or Cryptococcus.

30. The method of claim 29, wherein the subject is immunocompromised.

31. The method of any one of claims 8-30, wherein the subject is cross-protected against or treated for a disease or dysfunction selected from pulmonary disease, chronic obstructive pulmonary disease (COPD), poor pulmonary function, or a symptom thereof.

32. A kit for detecting, qualifying, or quantifying the level of an antibody directed against the Kex protein derived from Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens in a patient sample, the kit comprising a solid substrate having attached thereto a Kex peptide derived from one or more, two or more, three or more, or each of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens.

33. The kit of claim 32, further comprising a labeled detection molecule for detecting and measuring the level of the antibody that binds to the Kex peptides on the substrate.

34. The kit of claim 32 or claim 33, which is used for performing an immunoassay.

35. The kit of claim 34, wherein the immunoassay is an enzyme linked immunosorbent assay (ELISA).

36. The kit of any one of claims 32-35, further comprising a positive and/or a negative control for detecting, qualifying, or quantifying antibody levels.

37. A composition comprising a solid substrate and a plurality of Kex peptides derived from one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens immobilized on the substrate.

38. The composition of claim 36, wherein a Kex peptide from each of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens is immobilized at a different, indexable, location on the substrate.

39. The composition of claim 38, wherein a mixture of Kex peptides from two or more, three or more, or all four of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens is immobilized at a different, indexible, location on the substrate.

40. The composition of any one of claims 37-39, wherein the binding of an anti-Kex peptide antibody from a sample obtained from a subject can be measured or detected by measuring or detecting complexes of the anti-Kex peptide antibody bound to the Kex peptides localized on the substrate.

41. The composition of any one of claims 37-40, wherein the composition is contained in a kit for performing an immunoassay.

42. The composition of claim 41, wherein the immunoassay is an enzyme linked immunosorbent assay (ELISA).

43. A method of diagnosing a subject as being at risk of infection by one or more fungal pathogens and/or at risk of fungal-associated disease or symptoms thereof, the method comprising:

contacting a Kexin (Kex) protein or peptide derived from at least two of

Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens with a biological sample of the subject to detect an antibody or antigen binding fragment thereof in the sample that specifically binds to the Kex protein or peptide;

detecting the binding levels of the anti-Kex protein or peptide antibody or antigen binding fragment thereof in the sample to the Kex protein or peptide relative to control binding levels; and

diagnosing the subject as being at risk of infection or disease by the fungal pathogens when low or negligible levels of the Kex protein or peptide binding to antibody or antigen binding fragment are detected in the subject's sample relative to control levels, and diagnosing the subject as not being at risk of infection or disease by the fungal pathogens when moderate or high levels of the Kex protein or peptide binding to antibody or antigen binding fragment are detected in the subject's sample relative to control levels.

44. A method of stratifying a subject into a patient population that is at risk or that is not at risk of being infected by one or more fungal pathogens and/or at risk or not at risk of a fungal associated disease, the method comprising:

contacting a Kexin (Kex) protein or peptide derived from one or more fungal pathogens selected from Pneumocystis, Aspergillus, Candida, or Cryptococcus with a biological sample of the subject to detect an antibody or antigen binding fragment thereof in the sample that specifically binds to the Kex protein or peptide;

detecting and measuring levels of the antibody or antigen binding fragment thereof in the subject's sample that specifically binds to one or more of the fungal-derived Kex protein or peptide;

stratifying the subject into (i) a patient population that is at risk of having infection and/or disease associated with exposure to one or more of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens when low or negligible levels of anti-Kex protein or peptide antibody or antigen binding fragment thereof are detected and measured relative to a control, or (ii) a patient population that is not at risk of having infection and/or disease associated with exposure to one or more of the Pneumocystis, Aspergillus, Candida,

or Cryptococcus fungal pathogens when moderate or high levels of anti-Kex protein or peptide antibody or antigen binding fragment thereof are detected and measured relative to a control.

45. The method of claim 43 or claim 44, wherein the biological sample is blood, plasma, serum, or lymph.

46. The method of claim 45, wherein the biological sample is serum.

47. The method of any one of claims 43-46, wherein moderate to high levels or titers of specific mti-Pneumocystis Kex protein or peptide antibody or antigen binding fragment thereof in the subject's sample provide protection to the subject from infection and/or disease caused by one or more of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens.

48. The method of any one of claims 43-47, wherein a negative to low antibody titer range is from about 1 to about 3200 reciprocal endpoint antibody titers (RET), a moderate levels range is from about 3200 to about 12,800 RET, and a high level is greater than about 12,800 RET, based on the distribution of mti-Pneumocystis KEX1 RET in human samples.

49. The method of any one of claims 43-46, wherein the Kex protein or peptide is directly or indirectly coupled to a detectable substance.

50. The method of any one of claims 43-46, wherein the anti-Kex protein or peptide antibody or an antigen-binding fragment thereof bound to the Kex protein or peptide is detected by a secondary antibody or an antigen binding fragment thereof that is directly or directly coupled to a detectable substance selected from one or more of an enzyme, prosthetic group, fluorescent material, luminescent material, bioluminescent material, radioactive material, positron emitting metal, or a nonradioactive paramagnetic metal ion.

51. The method of any one of claims 43-46, 49, or 50, wherein the fungal-derived Kex protein or peptide is attached to or immobilized on a solid support.

52. The method of claim 51, wherein the binding of the anti-Kex protein or peptide antibody or antigen-binding fragment thereof in the subject's sample to the fungal-derived Kex protein or peptide is detected by an immunoassay.

53. The method of claim 43 or claim 44, further comprising treating the subject who has a low, no, or negligible level of an anti-fungal-derived Kex protein or peptide antibody or antigen binding fragment thereof in her/his sample with an antibody or an antigen binding fragment thereof directed against one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens so as to provide protection to the subject against infection and/or disease caused by the one or more fungal pathogens.

54. A method of treating or protecting an immunosuppressed patient against infection by one or more fungal pathogens and/or disease associated with infection by the fungal pathogens, the method comprising:

administering to a subject who is to receive, is receiving, or has received an immune suppressive drug or medication a peptide immunogen derived from the Kexin protein of a fungal pathogen, an isolated antiserum comprising an antibody produced against the peptide immunogen, or an isolated and purified antibody produced against the peptide immunogen, wherein the fungal pathogen is selected from one or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus in an amount effective for the patient to acquire cross-protective immunity against infection and/or disease associated with two or more of the Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogens.

55. The method of claim 54, wherein the patient is a pre-transplant patient or a post-transplant patient.

56. The method of claim 55, wherein the patient is to receive or has received a kidney, liver, heart, bone marrow, pancreas, lung, gall bladder, or bladder organ transplant.

57. The method of claim 54, wherein the patient suffers from rheumatoid arthritis or psoriasis.

58. The method of any one of claims 54-56, wherein the patient is to receive, is receiving, or has received one or more immunosuppressive drugs selected from corticosteroids, calcineurin inhibitors, mTOR inhibitors, inosine monophosphate dehydrogenase (IMDH) inhibitors, a biologic or a monoclonal antibody or an antigen binding fragments thereof.