Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2010 Oct 20;5(10):e13511. doi: 10.1371/journal.pone.0013511.

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

Author information

1
Medical Inflammation Research, Department of Experimental Medicine, Lund University, Lund, Sweden. Nandakumar.kutty-selva@ki.se

Erratum in

  • PLoS One. 2011;6(1). doi: 10.1371/annotation/90e60d13-28ac-4eed-8104-893bead21eb7. Ahooghalandari, Parvin [added]; Hellman, Lars [added].

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.

PMID:
20975959
PMCID:
PMC2958150
DOI:
10.1371/journal.pone.0013511
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center