A novel cystic fibrosis-mimetic Pseudomonas auxotrophic vaccine is protective in vivo and is associated with IL-17/IgA mucosal Immunity
Abstract
Pseudomonas aeruginosa (P.a) is a Gram-negative opportunistic pathogen that poses a major global health threat, particularly in immunocompromised individuals, patients with cystic fibrosis, and those with burn injuries or ventilator-associated pneumonia. Despite intense efforts, no vaccine is available for human use. In this context, live attenuated vaccines represent a promising but underexplored approach, offering the potential to elicit robust, long-lasting, and multifaceted immune responses including inducing trained immunity. Here, we sub-cultured ΔLasB-PAO1 (a P.a strain we have previously shown to have reduced virulence) in artificial sputum medium, a culture medium mimicking cystic fibrosis (CF) sputum in which bacteria often show auxotrophy. We showed that such strain ("V" for vaccine) was auxotrophic, less virulent, and had characteristics of "CF-like strains." Crucially, "V" induced both local (IgA) and systemic humoral responses as well as memory Th17 immune responses, and could, when administered in the lung, but not intra-muscularly, protect mice against a lethal PAO1-WT infection. Overall, the present study demonstrates that our vaccine formulation, in addition to providing an advantageous auxotrophic phenotype adapted to the CF setting, was efficient, when given mucosally and was associated with a pathway involving Th17 responses and secretory IgA, a critical barrier that neutralizes pathogens before tissue invasion.
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BibTeX
@article{sereme2026novel,
title = {{A novel cystic fibrosis-mimetic Pseudomonas auxotrophic vaccine is protective in vivo and is associated with IL-17/IgA mucosal Immunity}},
author = {Youssouf Sereme and Bérengère Villeret and Ségolène Caboche and Samuel Ikeh and Hugo Leroy and Delphine Beury and Florence Maurier and Christophe Desterke and Maëlys Born-Bony and Zhou Xing and Romé Voulhoux and Jean-Michel Sallenave},
journal = {Molecular Therapy},
year = {2026},
month = sep,
doi = {10.1016/j.ymthe.2026.06.029},
url = {https://amu.hal.science/hal-05767654v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A novel cystic fibrosis-mimetic Pseudomonas auxotrophic vaccine is protective in vivo and is associated with IL-17/IgA mucosal Immunity
AU - Youssouf Sereme
AU - Bérengère Villeret
AU - Ségolène Caboche
AU - Samuel Ikeh
AU - Hugo Leroy
AU - Delphine Beury
AU - Florence Maurier
AU - Christophe Desterke
AU - Maëlys Born-Bony
AU - Zhou Xing
AU - Romé Voulhoux
AU - Jean-Michel Sallenave
PY - 2026
DA - 2026/09/28
JO - Molecular Therapy
DO - 10.1016/j.ymthe.2026.06.029
UR - https://amu.hal.science/hal-05767654v1
AB - Pseudomonas aeruginosa (P.a) is a Gram-negative opportunistic pathogen that poses a major global health threat, particularly in immunocompromised individuals, patients with cystic fibrosis, and those with burn injuries or ventilator-associated pneumonia. Despite intense efforts, no vaccine is available for human use. In this context, live attenuated vaccines represent a promising but underexplored approach, offering the potential to elicit robust, long-lasting, and multifaceted immune responses including inducing trained immunity. Here, we sub-cultured ΔLasB-PAO1 (a P.a strain we have previously shown to have reduced virulence) in artificial sputum medium, a culture medium mimicking cystic fibrosis (CF) sputum in which bacteria often show auxotrophy. We showed that such strain ("V" for vaccine) was auxotrophic, less virulent, and had characteristics of "CF-like strains." Crucially, "V" induced both local (IgA) and systemic humoral responses as well as memory Th17 immune responses, and could, when administered in the lung, but not intra-muscularly, protect mice against a lethal PAO1-WT infection. Overall, the present study demonstrates that our vaccine formulation, in addition to providing an advantageous auxotrophic phenotype adapted to the CF setting, was efficient, when given mucosally and was associated with a pathway involving Th17 responses and secretory IgA, a critical barrier that neutralizes pathogens before tissue invasion.
SN - 1525-0016
SN - 1525-0024
ER -