A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.
OBJECTIVE
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.
Medical Inflammation Research, Department of Experimental Medicine, Lund University, Lund, Sweden. Nandakumar.kutty-selva@ki.se
Kutty Selva
KS
Nandakumar
Asa
A
Jansson
Bingze
B
Xu
Niclas
N
Rydell
Parvin
P
Ahooghalandari
Lars
L
Hellman
Anna M
AM
Blom
Rikard
R
Holmdahl
D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000276:immunology; D001168:Arthritis / Q000517:prevention & control*; D001483:Base Sequence; D002460:Cell Line; D015936:Complement C5a / Q000276:immunology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014614:Vaccines, Synthetic / Q000378:metabolism*
D057134:Antibodies, Neutralizing; D017931:DNA Primers; D014614:Vaccines, Synthetic; D015936:Complement C5a