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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1710802
- author
- Kutty Selva, Nandakumar
LU
; Jansson, Asa
; Xu, Bingze
; Rydell, Niclas
; Blom, Anna
LU
and Holmdahl, Rikard
LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 5
- issue
- 10
- article number
- e13511
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000283216400017
- pmid:20975959
- scopus:78149426505
- pmid:20975959
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0013511
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Protein Chemistry (013017510), Medical Inflammation Research (013212019)
- 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
- 2016-04-01 14:28:16
- date last changed
- 2022-01-28 00:46:26
@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.}},
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 (PLoS)}},
series = {{PLoS ONE}},
title = {{A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.}},
url = {{https://lup.lub.lu.se/search/files/3994270/1729687.pdf}},
doi = {{10.1371/journal.pone.0013511}},
volume = {{5}},
year = {{2010}},
}