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A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.

På svenska

Author

  • Nandakumar Kutty Selva
  • Asa Jansson
  • Bingze Xu
  • Niclas Rydell
  • Anna Blom
  • Rikard Holmdahl

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.

Department/s

Publishing year

2010

Language

English

Publication/Series

PLoS ONE

Volume

5

Issue

10

Document type

Journal article

Publisher

Public Library of Science (PLoS)

Topic

  • Immunology in the medical area
  • Other Basic Medicine

Status

Published

Research group

  • Immunology
  • Protein Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1932-6203