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

Kutty Selva, Nandakumar LU ; Jansson, Asa; Xu, Bingze; Rydell, Niclas; Blom, Anna LU and Holmdahl, Rikard LU (2010) In PLoS ONE 5(10).
Abstract
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... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
5
issue
10
publisher
Public Library of Science
external identifiers
  • wos:000283216400017
  • pmid:20975959
  • scopus:78149426505
ISSN
1932-6203
DOI
10.1371/journal.pone.0013511
language
English
LU publication?
yes
id
fd141ef4-375b-4be0-b0a1-582357ba6e5b (old id 1710802)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20975959?dopt=Abstract
date added to LUP
2010-11-05 13:53:50
date last changed
2018-06-10 04:20:29
@article{fd141ef4-375b-4be0-b0a1-582357ba6e5b,
  abstract     = {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.},
  articleno    = {e13511},
  author       = {Kutty Selva, Nandakumar and Jansson, Asa and Xu, Bingze and Rydell, Niclas and Blom, Anna and Holmdahl, Rikard},
  issn         = {1932-6203},
  language     = {eng},
  number       = {10},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0013511},
  volume       = {5},
  year         = {2010},
}