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A recombinant vacci...
A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.
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- Kutty Selva, Nandakumar (författare)
- Karolinska Institutet,Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden; Karolinska Institutet, Stockholm, Sweden
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- Jansson, Asa (författare)
- Resistentia Pharmaceuticals AB, Uppsala, Sweden
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- Xu, Bingze (författare)
- Resistentia Pharmaceuticals AB, Uppsala, Sweden
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- Rydell, Niclas (författare)
- Resistentia Pharmaceuticals AB, Uppsala, Sweden; Phadia AB, Uppsala, Sweden
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- Blom, Anna (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups,Department of Laboratory Medicine, Lund University, Skane University Hospital, Malmö, Sweden
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- Holmdahl, Rikard (författare)
- Karolinska Institutet,Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden; Karolinska Institutet, Stockholm, Sweden
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(creator_code:org_t)
- 2010-10-20
- 2010
- Engelska.
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Ingår i: PLoS ONE. - San Francisco, CA : Public Library of Science (PLoS). - 1932-6203. ; 5:10
- Relaterad länk:
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https://portal.resea... (primary) (free)
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10... (free)
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https://journals.plo...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- OBJECTIVES: To develop and validate a recombinant vaccine to attenuate inflammation in arthritis by sustained neutralization of the anaphylatoxin C5a. METHODS: We constructed and expressed fusion protein of C5a and maltose binding protein. Efficacy of specific C5a neutralization was tested using the fusion protein as vaccine in three different arthritis mouse models: collagen induced arthritis (CIA), chronic relapsing CIA and collagen antibody induced arthritis (CAIA). Levels of anti-C5a antibodies and anti-collagen type II were measured by ELISA. C5a neutralization assay was done using a rat basophilic leukemia cell-line transfected with the human C5aR. Complement activity was determined using a hemolytic assay and joint morphology was assessed by histology. RESULTS: Vaccination of mice with MBP-C5a led to significant reduction of arthritis incidence and severity but not anti-collagen antibody synthesis. Histology of the MBP-C5a and control (MBP or PBS) vaccinated mice paws confirmed the vaccination effect. Sera from the vaccinated mice developed C5a-specific neutralizing antibodies, however C5 activation and formation of the membrane attack complex by C5b were not significantly altered. CONCLUSIONS: Exploitation of host immune response to generate sustained C5a neutralizing antibodies without significantly compromising C5/C5b activity is a useful strategy for developing an effective vaccine for antibody mediated and C5a dependent inflammatory diseases. Further developing of such a therapeutic vaccine would be more optimal and cost effective to attenuate inflammation without affecting host immunity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Publikations- och innehållstyp
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