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dc.contributor.author
Campodónico, Victoria L.
dc.contributor.author
Llosa, Nicolas J.
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Bentancor, Leticia Verónica
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Maira-Litran, Tomas
dc.contributor.author
Pier, Gerald B.
dc.date.available
2023-03-31T18:41:35Z
dc.date.issued
2011-08
dc.identifier.citation
Campodónico, Victoria L.; Llosa, Nicolas J.; Bentancor, Leticia Verónica; Maira-Litran, Tomas; Pier, Gerald B.; Efficacy of a conjugate vaccine containing polymannuronic acid and flagellin against experimental Pseudomonas aeruginosa lung infection in mice; American Society for Microbiology; Infection and Immunity; 79; 8; 8-2011; 3455-3464
dc.identifier.issn
0019-9567
dc.identifier.uri
http://hdl.handle.net/11336/192359
dc.description.abstract
Vaccines that could effectively prevent Pseudomonas aeruginosa pulmonary infections in the settings of cystic fibrosis (CF) and nosocomial pneumonia could be exceedingly useful, but to date no effective immunotherapy targeting this pathogen has been successfully developed for routine use in humans. Evaluations using animals and limited human trials of vaccines and their associated immune effectors against different P. aeruginosa antigens have suggested that antibody to the conserved surface polysaccharide alginate, as well as the flagellar proteins, often give high levels of protection. However, alginate itself does not elicit protective antibody in humans, and flagellar vaccines containing the two predominant serotypes of this antigen may not provide sufficient coverage against variant flagellar types. To evaluate if combining these antigens in a conjugate vaccine would be potentially efficacious, we conjugated polymannuronic acid (PMA), containing the blocks of mannuronic acid conserved in all P. aeruginosa alginates, to type a flagellin (FLA) and evaluated immunogenicity, opsonic killing activity, and passive protective efficacy in mice. The PMA-FLA conjugate was highly immunogenic in mice and rabbits and elicited opsonic antibodies against mucoid but not nonmucoid P. aeruginosa, but nonetheless rabbit antibody to PMA-FLA showed evidence of protective efficacy against both types of this organism in a mouse lung infection model. Importantly, the PMA-FLA conjugate vaccine did not elicit antibodies that neutralized the Toll-like receptor 5 (TLR5)-activating activity of flagellin, an important part of innate immunity to flagellated microbial pathogens. Conjugation of PMA to FLA appears to be a promising path for developing a broadly protective vaccine against P. aeruginosa.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Microbiology
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CONJUGATE VACCINE
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PSEUDOMONAS AERUGINOSA
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LUNG INFECTION
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Enfermedades Infecciosas
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Efficacy of a conjugate vaccine containing polymannuronic acid and flagellin against experimental Pseudomonas aeruginosa lung infection in mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-03-30T14:44:34Z
dc.journal.volume
79
dc.journal.number
8
dc.journal.pagination
3455-3464
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Washington D.C
dc.description.fil
Fil: Campodónico, Victoria L.. Brigham And Women's Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Llosa, Nicolas J.. Brigham And Women's Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Bentancor, Leticia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Brigham And Women's Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Maira-Litran, Tomas. Brigham And Women's Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Pier, Gerald B.. Brigham And Women's Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
dc.journal.title
Infection and Immunity
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/IAI.00157-11
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/IAI.00157-11
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