A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.
Författare
Summary, in English
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.
Avdelning/ar
- Immunology
- Proteinkemi, Malmö
Publiceringsår
2010
Språk
Engelska
Publikation/Tidskrift/Serie
PLoS ONE
Volym
5
Issue
10
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Public Library of Science (PLoS)
Ämne
- Immunology in the medical area
- Other Basic Medicine
Status
Published
Forskningsgrupp
- Immunology
- Protein Chemistry, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1932-6203