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

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.

• Authors: Kutty Selva Nandakumar, Asa Jansson, Bingze Xu, Niclas Rydell, Parvin Ahooghalandari, Lars Hellman, Anna M Blom, Rikard Holmdahl
• Journal: PloS one (PLoS One) Vol. 5 Issue 10 Pg. e13511 (Oct 20 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20975959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• DNA Primers
• Vaccines, Synthetic
• Complement C5a

Topics

• Animals
• Antibodies, Neutralizing (biosynthesis, immunology)
• Arthritis (prevention & control)
• Base Sequence
• Cell Line
• Complement C5a (immunology)
• DNA Primers
• Enzyme-Linked Immunosorbent Assay
• Mice
• Mice, Inbred BALB C
• Reverse Transcriptase Polymerase Chain Reaction
• Vaccines, Synthetic (metabolism)