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Construction and pr...
Construction and preclinical evaluation of mmCT, a novel mutant cholera toxin adjuvant that can be efficiently produced in genetically manipulated Vibrio cholerae
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- Lebens, Michael, 1956 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Terrinoni, Manuela (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Karlsson, S. L. (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Larena, Maximilian (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Gustafsson-Hedberg, T. (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Källgård, Susanne (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Nygren, Erik (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Holmgren, Jan, 1944 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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(creator_code:org_t)
- Elsevier Ltd, 2016
- 2016
- Engelska.
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Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 34:18, s. 2121-2128
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- There is an urgent need for new adjuvants that are effective with mucosally administered vaccines. Cholera toxin (CT) is the most powerful known mucosal adjuvant but is much too toxic for human use. In an effort to develop a useful mucosal adjuvant we have generated a novel non-toxic mutant CT molecule that retains much of the adjuvant activity of native CT. This was achieved by making the enzymatically active A subunit (CTA) recalcitrant to the site-specific proteolytic cleavage ("nicking") required for toxicity, which was found to require mutations not only in the two residues rendering the molecule resistant to trypsin but also in neighboring sites protecting against cleavage by Vibrio cholerae proteases. This multiple-mutated CT (mmCT) adjuvant protein could be efficiently produced in and purified from the extracellular medium of CT-deleted V. cholerae. The mmCT completely lacked detectable enterotoxicity in an infant mouse model and had >1000-fold reduced cAMP inducing activity compared to native CT in a sensitive mammalian target cell system. It nonetheless proved to have potent adjuvant activity on mucosal and systemic antibody as well as cellular immune responses to mucosally co-administered antigens including oral cholera and intranasal influenza vaccines. We conclude that mmCT is an attractive novel non-toxic mucosal adjuvant for enhancing immune responses to co-administered mucosal vaccines
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- Adjuvant
- Cholera toxin
- Mucosal immunity
- Mucosal vaccine
- cholera vaccine
- cyclic AMP
- immunoglobulin A
- immunoglobulin G
- influenza vaccine
- proteinase
- trypsin
- bacterium antibody
- immunological adjuvant
- mutant protein
- animal experiment
- animal model
- antibody blood level
- Article
- CD4+ T lymphocyte
- CD8+ T lymphocyte
- cellular immunity
- cholera
- controlled study
- enzyme linked immunosorbent assay
- flow cytometry
- immune response
- mouse
- nonhuman
- priority journal
- thymocyte
- Vibrio cholerae
- animal
- blood
- chemistry
- female
- genetics
- humoral immunity
- immunology
- metabolism
- mutation
- toxicity testing
- Adjuvants
- Immunologic
- Animals
- Antibodies
- Bacterial
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- Cholera Vaccines
- Immunity
- Cellular
- Immunity
- Humoral
- Immunity
- Mucosal
- Influenza Vaccines
- Mice
- Mutant Proteins
- Toxicity Tests
- Adjuvant
- Cholera toxin
- Mucosal immunity
- Mucosal vaccine
- enterotoxigenic escherichia-coli
- b-subunit
- vaccine development
- recent
- progress
- dmlt adjuvant
- etec vaccine
- t-cells
- immunogenicity
- generation
- antibodies
- Immunology
- Research & Experimental Medicine
- lorenzo v
- 1994
- bacterial pathogenesis
- pt a
- v235
- p386
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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