Anti-microbial immunomodulation
Inventors
Gunn, Harold David • Dhanji, Salim • Mullins, David W.
Assignees
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Publication Number
US-11819543-B2
Publication Date
2023-11-21
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 anti-microbial immunomodulation by modulating an immune system in a vertebrate host using a site specific immunomodulator. An antigenic formulation comprising antigenic determinants is administered for therapeutic or prophylactic treatment to affect a localized immune response in a target tissue or organ, where the host is identified as being at risk for infection by a first microbial pathogen in the same target tissue or organ.
The antigenic formulation includes antigenic determinants specific for a heterologous microbial pathogen, selected from whole cells or cell wall extracts, including whole killed organisms or whole killed organisms-derived antigenic material such as heat-inactivated or phenol-inactivated antigenic preparations. The document describes mapping endogenous flora domains to tissue and organ pathogenicity, with links between tissue and organ sites and common acute bacterial and viral pathogens.
The invention further includes immune response monitoring using immune cell types and cytokine measurements, as well as differential gene expression. It relates immune modulation to macrophage activation state, including M1-like macrophages and M2-like macrophages, and to measured markers including Nos2 and CD206.
The document provides exemplary site-specific immune recruitment and prophylaxis using antigenic formulations. It describes increased monocyte/macrophage and dendritic cell populations in lungs, organ- and pathogen-specific leukocyte recruitment, prophylactic protection in lungs against Streptococcus pneumoniae and Pseudomonas aeruginosa, antimicrobial therapy in inflammatory bowel disease via killed Escherichia coli formulations, peritoneal prophylaxis against Salmonella enterica, and skin prophylaxis against Pseudomonas aeruginosa using Staphylococcus aureus-derived formulations.
Claims Coverage
The independent claim coverage centers on one prophylactic method with immune-system modulation in a vertebrate host, using an antigenic formulation with antigenic determinants specific for a heterologous microbial pathogen. The inventive features include Escherichia coli-specific determinants, selection from whole cells or cell wall extracts, target tissue context linked to gastrointestinal tract or peritoneal cavity infection, and successive dosing over a defined interval and duration.
Immune-system modulation for prophylactic treatment at risk in a vertebrate host
A method of modulating an immune system in a vertebrate host for prophylactic treatment of infection by a first microbial pathogen in a target tissue, wherein the host has been identified as being at risk for infection by the first microbial pathogen.
Administering an SSI antigenic formulation with determinants for a heterologous microbial pathogen
Administering an effective amount of an antigenic formulation comprising antigenic determinants specific for a second heterologous microbial pathogen.
Escherichia coli-specific antigenic determinants
Wherein the second heterologous microbial pathogen is Escherichia coli.
Whole cells or cell wall extracts as antigenic determinant sources
Wherein the antigenic determinants are selected from the group consisting of whole cells or cell wall extracts.
Target tissue context linked to gastrointestinal tract or peritoneal cavity infection
Wherein the first microbial pathogen is a gastrointestinal tract pathogen and the target tissue is the gastrointestinal tract; or the first microbial pathogen is a pathogen of a peritoneal cavity organ and the target tissue is the peritoneal cavity.
Successive dosing interval and prophylactic duration
Wherein the 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 claim coverage centers on prophylactic immune-system modulation in a vertebrate host using an SSI antigenic formulation with Escherichia coli-specific antigenic determinants, restricted to whole cells or cell wall extracts, tied to either gastrointestinal tract or peritoneal cavity pathogen or tissue contexts, and delivered as successive doses over a defined interval and duration.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Site-specific immune recruitment and prophylaxis, including increased monocyte/macrophage and dendritic cell populations in lungs and organ- and pathogen-specific leukocyte recruitment.
Prophylactic protection in lungs against Streptococcus pneumoniae and Pseudomonas aeruginosa.
Antimicrobial therapy in inflammatory bowel disease via killed Escherichia coli formulations.
Prophylaxis against Salmonella enterica via intraperitoneal prophylaxis.
Skin prophylaxis against Pseudomonas aeruginosa using Staphylococcus aureus-derived formulations.
Antiviral prophylaxis in lungs using bacterial SSI formulations against MHV68 with reduced luminescence.
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