ArticleInfection and immunity2002
Construction and characterization of a live, attenuated aroA deletion mutant of Pseudomonas aeruginosa as a candidate intranasal vaccine.
Article in Infection and immunity, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- A novel cystic fibrosis-mimetic Pseudomonas auxotrophic vaccine is protective in vivo and is associated with IL-17/IgA mucosal Immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
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- Live auxotrophic vaccines contribute to protection against chronic lung infections caused byFrontiers in immunology · 2026Article
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- A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections.Nature communications · 2024Article
- Why is manganese so valuable to bacterial pathogens?Frontiers in cellular and infection microbiology · 2023Review
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- EPSP Synthase-Depleted Cells Are Aromatic Amino Acid Auxotrophs in Mycobacterium smegmatis.Microbiology spectrum · 2021Article
- AVaccines · 2021Article
- Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia.Infection and immunity · 2021Article
- Targeted Genome Reduction ofFrontiers in bioengineering and biotechnology · 2021Article
- UnderstandingCells · 2020Review
- Role of Pseudomonas aeruginosa Glutathione Biosynthesis in Lung and Soft Tissue Infection.Infection and immunity · 2020Article
- Generation of a highly attenuated strain of Pseudomonas aeruginosa for commercial production of alginate.Microbial biotechnology · 2020Article
- MicroRNA-302/367 Cluster Impacts Host Antimicrobial Defense via Regulation of Mitophagic Response AgainstFrontiers in immunology · 2020Article
- Amino Acid Biosynthetic Pathways Are Required forAntimicrobial agents and chemotherapy · 2019Article
- Single-Stranded DNA-Binding Protein and Exogenous RecBCD Inhibitors Enhance Phage-Derived Homologous Recombination in Pseudomonas.iScience · 2019Article
- Article
- A D-Alanine auxotrophic live vaccine is effective against lethal infection caused by Staphylococcus aureus.Virulence · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Antibodies to the lipopolysaccharide O antigen of Pseudomonas aeruginosa mediate high-level immunity, but protective epitopes have proven to be poorly immunogenic, while nonprotective or minimally protective O-antigen epitopes often elicit the best immune responses. With the goal of developing a broadly protective P. aeruginosa vaccine, we used a gene replacement system based on the Flp recombinase to construct an unmarked aroA deletion mutant of the P. aeruginosa serogroup O2/O5 strain PAO1. The resultant aroA deletion mutant of PAO1 is designated PAO1 Delta aroA. The aroA deletion was confirmed by both PCR and failure of the mutant to grow on minimal media lacking aromatic amino acids. When evaluated for safety and immunogenicity in mice, PAO1 Delta aroA could be applied either intranasally or intraperitoneally at doses up to 5 x 10(9) CFU per mouse without adverse effects. No dissemination of PAO1 Delta aroA to blood, liver, or spleen was detected after intranasal application, and histological evidence of pneumonia was minimal. Intranasal immunization of mice and rabbits elicited high titers of immunoglobulin G to whole bacterial cells and to heat-stable bacterial antigens of all seven prototypic P. aeruginosa serogroup O2/O5 strains. The mouse antisera mediated potent phagocytic killing of most of the prototypic serogroup O2/O5 strains, while the rabbit antisera mediated phagocytic killing of several serogroup-heterologous strains in addition to killing all O2/O5 strains. This live, attenuated P. aeruginosa strain PAO1 Delta aroA appears to be safe for potential use as an intranasal vaccine and elicits high titers of opsonic antibodies against multiple strains of the P. aeruginosa O2/O5 serogroup.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.