Anti-microbial immunomodulation
Inventors
Gunn, Harold David • Dhanji, Salim • Mullins, David W.
Assignees
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Publication Number
US-10251946-B2
Publication Date
2019-04-09
Expiration Date
Abstract
The invention provides methods of modulating an immune system in a vertebrate host for the therapeutic or prophylactic treatment of infection by a first microbial pathogen in a target tissue, comprising administration at an administration site of an effective amount of an antigenic formulation comprising antigenic determinants specific for a second heterologous microbial pathogen.
Core Innovation
The invention relates to a method of modulating an immune system in a vertebrate host for the prophylactic treatment of infection by a first microbial pathogen in a target tissue. The method administers an antigenic formulation comprising antigenic determinants specific for a second heterologous microbial pathogen, and the antigenic determinants are selected from whole cells or cell wall extracts.
The disclosed approach supports tissue or organ-specific prophylaxis by selecting antigenic determinants corresponding to heterologous microbial pathogens associated with specific tissues. The document maps endogenous flora domains and tissues to tissue or organ sites of pathogens, including contiguous spread and bacteremic spread, and links this mapping to selection of immunogenic compositions tailored to the target tissue.
The summarized disclosure further reports antigenic formulations that induce tissue-targeted immune activity and provide prophylaxis against heterologous challenges in lungs and other tissues. The approach is supported by immune-response characterization, including inflammatory monocytes, dendritic cells, CD4+ T cells, CD8+ T cells, NK cells, and macrophage M1-like versus M2-like states using markers such as Nos2 and CD206.
Claims Coverage
The independent claims cover a prophylactic immune-modulation method for a vertebrate host, using antigenic determinants specific for a second heterologous microbial pathogen in a target tissue. The inventive features are: heterologous-pathogen antigenic determinants for target tissue prophylaxis; whole cells or cell wall extracts as the antigenic determinants; defined lung and skin pathogen-to-tissue pairings; and a successive dosing schedule with at least one hour intervals over a defined time window and minimum duration.
Target tissue prophylactic immune modulation with heterologous-pathogen antigenic determinants
A method of modulating an immune system in a vertebrate host for the prophylactic treatment of infection by a first microbial pathogen in a target tissue by administering an antigenic formulation comprising antigenic determinants specific for a second heterologous microbial pathogen.
Whole cells or cell wall extracts as antigenic determinants
The antigenic determinants are selected from the group consisting of whole cells or cell wall extracts.
Lung-specific pathogen-to-antigen/tissue pairing for prophylaxis
The first microbial pathogen is Streptococcus pneumonia or Pseudomonas aeruginosa, the second heterologous microbial pathogen is Klebsiella pneumonia, and the target tissue is the lung; or the first microbial pathogen is a viral lung pathogen, the second heterologous microbial pathogen is Klebsiella pneumonia, and the target tissue is the lung.
Skin-specific pathogen-to-antigen/tissue pairing for prophylaxis
The first microbial pathogen is P. aeruginosa, the second heterologous microbial pathogen is S. aureus, and the target tissue is the skin.
Successive dosing schedule over a defined period and minimum duration
Administering comprises administering successive doses of the formulation at a dosage interval of at least one hour, so that two or more doses are administered over a period from 2 days to 1 month, over a dosage duration of at least one week.
The claims cover target-tissue prophylactic immune modulation in a vertebrate host using antigenic determinants specific to a heterologous microbial pathogen. Coverage is constrained by selected determinant types, explicit first and second pathogen-to-tissue pairings, and a successive dosing regimen with two or more doses over 2 days to 1 month and at least one week minimum duration.
Stated Advantages
Documented Applications
No documented applications found
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