A live auxotrophic vaccine confers mucosal immunity and protection against lethal pneumonia caused by Pseudomonas aeruginosa

Autor: Germán Bou, Miriam Moscoso, Patricia García, Víctor Fuentes-Valverde, Manuel Vilanova, Fátima Gärtner, Juan A. Vallejo, Alexandra Correia, Mónica Francisco-Tomé, Maria P Cabral, Astrid Pérez
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Pulmonology
Physiology
Respiratory System / immunology
Respiratory System
medicine.disease_cause
Biochemistry
White Blood Cells
Mice
Animal Cells
Immune Physiology
Medicine and Health Sciences
Public and Occupational Health
Biology (General)
Respiratory Tract Infections / immunology
Pathogen
Pneumonia
Bacterial / immunology
Respiratory Tract Infections
Routes of Administration
0303 health sciences
Vaccines
Innate Immune System
Mice
Inbred BALB C
Attenuated vaccine
Immune System Proteins
biology
T Cells
Immunogenicity
030302 biochemistry & molecular biology
Vaccination and Immunization
Antibodies
Bacterial
3. Good health
medicine.anatomical_structure
Infectious Diseases
Pseudomonas aeruginosa
Cytokines
Female
Antibody
Cellular Types
Research Article
Vaccines
Attenuated / pharmacology
Infectious Disease Control
QH301-705.5
Immune Cells
Immunology
Spleen
Pseudomonas aeruginosa / immunology
Vaccines
Attenuated
Microbiology
Antibodies
03 medical and health sciences
Immunity
Virology
Genetics
medicine
Pneumonia
Bacterial
Vaccines
Attenuated / immunology
Animals
Pseudomonas Infections
Molecular Biology
Immunity
Mucosal
Administration
Intranasal
030304 developmental biology
Pharmacology
Blood Cells
Pseudomonas aeruginosa / pathogenicity
Biology and Life Sciences
Proteins
Cell Biology
Pneumonia
Molecular Development
RC581-607
medicine.disease
Pseudomonas aeruginosa / metabolism
Immune System
biology.protein
Parasitology
Preventive Medicine
Immunologic diseases. Allergy
Pseudomonas Infections / immunology
Antibodies
Bacterial / immunology
Developmental Biology
Zdroj: PLoS Pathogens, Vol 16, Iss 2, p e1008311 (2020)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Pseudomonas aeruginosa is one of the leading causes of nosocomial pneumonia and its associated mortality. Moreover, extensively drug-resistant high-risk clones are globally widespread, presenting a major challenge to the healthcare systems. Despite this, no vaccine is available against this high-concerning pathogen. Here we tested immunogenicity and protective efficacy of an experimental live vaccine against P. aeruginosa pneumonia, consisting of an auxotrophic strain which lacks the key enzyme involved in D-glutamate biosynthesis, a structural component of the bacterial cell wall. As the amounts of free D-glutamate in vivo are trace substances in most cases, blockage of the cell wall synthesis occurs, compromising the growth of this strain, but not its immunogenic properties. Indeed, when delivered intranasally, this vaccine stimulated production of systemic and mucosal antibodies, induced effector memory, central memory and IL-17A-producing CD4+ T cells, and recruited neutrophils and mononuclear phagocytes into the airway mucosa. A significant improvement in mice survival after lung infection caused by ExoU-producing PAO1 and PA14 strains was observed. Nearly one third of the mice infected with the XDR high-risk clone ST235 were also protected. These findings highlight the potential of this vaccine for the control of acute pneumonia caused by this bacterial pathogen.
Author summary Pseudomonas aeruginosa is an opportunistic bacterium and one of the most common causes of healthcare-associated diseases, including acute pneumonia, causing high mortality within immunocompromised hosts. Most of these infections are strikingly difficult to treat using conventional antibiotic therapies, since this microorganism displays high intrinsic resistance to a wide range of antibiotics. Moreover, to date, no vaccine is available for prevention. Here we used a mutated bacterial strain, which is unable to replicate in vivo and to cause disease, as a live vaccine against acute pneumonia caused by this pathogen. When applied intranasally, this vaccine induced immunity both at local and distant body sites, activating immune cells which were recruited into the airway mucosa. This evoked immune response reduced the number of non-surviving mice after infection with two cytotoxic P. aeruginosa strains causing acute lung infection. Some protection was also observed against an internationally disseminated cytotoxic strain. These data indicate that this is a promising vaccine candidate against P. aeruginosa-pneumonia.
Databáze: OpenAIRE
Externí odkaz: