Treatment and detection of infection and disease associated with different fungal pathogens
Inventors
Norris, Karen A. • Rabacal, Whitney • RAYENS, EMILY
Assignees
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Publication Number
US-12453761-B2
Publication Date
2025-10-28
Expiration Date
Abstract
Described are immunogenic compositions comprising a non-naturally occurring pan-fungal Kex peptide, and methods of using such compositions for the treatment or prevention of infection and/or diseases associated with fungal pathogens (e.g., Pneumocystis, Aspergillus, Candida, or Cryptococcus) in the subject. Also provided are compositions and kits for detecting or quantifying the presence of antibodies directed against a non-naturally occurring pan-fungal Kex peptide in a subject.
Core Innovation
The described invention provides immunogenic non-naturally occurring pan-fungal Kex peptides, including Pan-fungal peptide 2 set forth in SEQ ID NO: 2, and polynucleotides encoding the peptides. An immunogenic composition includes an effective amount of the pan-fungal Kex peptide or the polynucleotide together with a pharmaceutically acceptable carrier or excipient, and is used to elicit an immune response in a subject.
The immune response includes the production of antiserum comprising isolatable antibodies that specifically react with Pan-fungal peptide 2 and with kexin peptides of fungal pathogens. The invention addresses fungal infections and associated pulmonary disease by administering the immunogenic composition to treat or protect a subject against fungal infection, including Pneumocystis pneumonia (PCP), aspergillosis, and Invasive Pulmonary Aspergillosis (IPA).
The fungal pathogens explicitly include Aspergillus, Candida, Cryptococcus, and Pneumocystis, and the described subject populations include immunocompromised and immunosuppressed subjects, including pre-transplant and post-transplant subjects. The disclosure further describes diagnostic and monitoring approaches and kits that detect and quantify anti-pan-fungal Kex peptide antibodies in samples, with ELISA and multiplex formats to stratify patients and guide directed prophylactic or therapeutic decisions.
Claims Coverage
The independent claims cover methods of eliciting an immune response and methods of treating or protecting against a fungal infection, each centered on administering an immunogenic composition containing Pan-fungal peptide 2 (SEQ ID NO: 2) or a polynucleotide encoding it, with a pharmaceutically acceptable carrier or excipient. The inventive features include antibody production specific to Pan-fungal peptide 2 and cross-reactive kexin peptides from selected fungal pathogens, with optional refinements directed to subject population and pulmonary disease indications.
Administering pan-fungal peptide 2 or encoding polynucleotide to elicit an immune response
A method of eliciting an immune response in a subject by administering an immunogenic composition comprising an effective amount of an immunogenic peptide having at least about 95% or more amino acid sequence identity to Pan-fungal peptide 2 (SEQ ID NO: 2) or a polynucleotide encoding the peptide, and a pharmaceutically acceptable carrier or excipient.
Treating or protecting against fungal infection using pan-fungal peptide 2 immunogenic composition
A method of treating or protecting a subject against a fungal infection by administering an immunogenic composition comprising an effective amount of an immunogenic peptide having at least about 95% or more amino acid sequence identity to Pan-fungal peptide 2 (SEQ ID NO: 2) or a polynucleotide encoding the peptide, and a pharmaceutically acceptable carrier or excipient.
Eliciting antiserum with isolatable antibodies cross-reacting with kexin peptides of selected fungal pathogens
The immunogenic composition elicits in the subject the production of antiserum comprising isolatable antibodies that specifically react with Pan-fungal peptide 2 and with kexin peptides of one or more fungal pathogens selected from Aspergillus, Candida, Cryptococcus, or Pneumocystis fungal pathogens.
Across the independent claims, the core coverage is methods that administer an immunogenic composition containing Pan-fungal peptide 2 (SEQ ID NO: 2) or a polynucleotide encoding it to elicit an immune response and/or treat or protect against fungal infection. A central aspect is production of antiserum containing isolatable antibodies that specifically react with Pan-fungal peptide 2 and cross-react with kexin peptides from selected fungal pathogens (Aspergillus, Candida, Cryptococcus, and/or Pneumocystis).
Stated Advantages
Reduced Pneumocystis pneumonia or colonization in SIV-infected non-human primates.
Reduced invasive pulmonary aspergillosis mortality and fungal burden in immunosuppressed mice.
Documented Applications
Diagnosis and monitoring through detection and quantification of anti-pan-fungal Kex peptide antibodies in samples.
Patient stratification and directed prophylactic or therapeutic decisions using immunoassay formats such as ELISA and multiplex formats.
Treatment or protection against fungal infection, including Pneumocystis pneumonia (PCP), aspergillosis, and Invasive Pulmonary Aspergillosis (IPA).
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