Killed but metabolically active Pseudomonas aeruginosa-based vaccine induces protective humoral- and cell-mediated immunity against Pseudomonas aeruginosa pulmonary infections |
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| Affiliation: | 1. Univ Grenoble Alpes, CNRS, CHU Grenoble, Grenoble INP, TIMC-IMAG UMR 5525, 38000 Grenoble, France;2. Etablissement Français du Sang, BP35, 38701 La Tronche, France;1. Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, NIAID, NIH, USA;2. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA;3. MedImmune Vaccines, Mountain View, CA, USA;1. University of Pennsylvania, Perelman School of Medicine, Department of Microbiology, Philadelphia, PA, USA;2. Gautam Buddha University, School of Biotechnology, Greater Noida, Yamuna Expressway, Uttar Pradesh, India;1. Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;2. Quality Control Department of Iran Gelatin Capsule Mfg. Co., Tehran, Iran;3. Burn Research Center, Hazrat Fatima Hospital, Iran University of Medical Sciences, Tehran, Iran;4. Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, PR China;2. Institute of Materia Medica, North Sichuan Medical College, Nanchong 637007, PR China;3. Department of Orthopaedics, Chongqing General Hospital, Chongqing 400014, PR China;1. Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran;2. Department of Microbiology, Tehran University of Medical Sciences, Tehran, Iran;3. Department of Microbiology, Iran University of Medical Sciences, Tehran, Iran;4. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran;5. Shiraz HIV/AIDS Research Center (SHARC), Shiraz, Iran |
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| Abstract: | Pseudomonas aeruginosa (Pa) is a significant cause of morbidity and mortality, especially in cystic fibrosis patients. Its eradication is difficult due to a wide phenotypic adaptability and an increase of its resistance to antibiotics. After the failure of several recombinant vaccines which mainly triggered humoral response, live-attenuated vaccines received attention thanks to their ability to elicit a broad immunity with both humoral- and cell-mediated responses, essential to fight this pathogen. In this study, we developed an innovative and safer live-attenuated Pa vaccine based on a Killed But Metabolically Active (KBMA) attenuation method. KBMA Pa has been further rationally designed to overexpress beneficial effectors like the type 3 secretion system apparatus. We demonstrated that KBMA Pa elicits a high and broad humoral response in mice against several antigens of particular interest such as OprF and PcrV proteins. Moreover, we assessed cytokines in the serum of immunized mice and showed that KBMA Pa elicits Th1, Th2 and especially Th17 pathways of cell-mediated immune responses. Th17 pathway involvement was also confirmed after specific stimulation of helper T cells in immunized mice. Finally, we showed that this vaccine is safe and has a protective effect in a murine acute pulmonary infectious challenge. In conclusion, KBMA Pa is a new platform with high potential for the development of a vaccine against Pa. |
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| Keywords: | Vaccine Killed but metabolically active Infectious disease Cystic fibrosis Th17 |
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