A Recombinant Vaccine Effectively Induces C5a-Specific Neutralizing Antibodies and Prevents Arthritis 英文参考文献.docVIP
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A Recombinant Vaccine Effectively Induces C5a-Specific Neutralizing Antibodies and Prevents Arthritis 英文参考文献
ARecombinantVaccineEffectivelyInducesC5a-Specific
NeutralizingAntibodiesandPreventsArthritis
KuttySelvaNandakumar1,2*,Asa? Jansson3,BingzeXu3,NiclasRydell3¤,AnnaM.Blom4 ,Rikard
Holmdahl1,2
1Medical Inflammation Research, Department of Experimental Medicine, Lund University, Lund, Sweden, 2Medical Inflammation Research, Department of Medical
Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden, 3Resistentia Pharmaceuticals AB, Uppsala, Sweden, 4Section of Medical Protein Chemistry,
DepartmentofLaboratoryMedicine,LundUniversity,Ska?ne UniversityHospital,Malmo¨,Sweden
Abstract
Objectives: To develop and validate a recombinant vaccine to attenuate inflammation in arthritis by sustained
neutralizationoftheanaphylatoxinC5a.
Methods: We constructed and expressed fusion protein of C5a and maltose binding protein. Efficacy of specific C5a
neutralizationwastestedusingthefusionproteinasvaccineinthreedifferentarthritismousemodels:collageninducedarthritis
(CIA),chronicrelapsingCIAandcollagenantibodyinducedarthritis(CAIA).Levelsofanti-C5aantibodiesandanti-collagentypeII
weremeasuredbyELISA.C5aneutralizationassaywasdoneusingaratbasophilicleukemiacell-linetransfectedwiththehuman
C5aR.Complementactivitywasdeterminedusingahemolyticassayandjointmorphologywasassessedbyhistology.
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
vaccinationeffect.SerafromthevaccinatedmicedevelopedC5a-specificneutralizingantibodies,howeverC5activationand
formationofthemembraneattackcomplexbyC5bwerenotsignificantlyaltered.
Conclusions:ExploitationofhostimmuneresponsetogeneratesustainedC5aneutralizingantibodieswithoutsignificantly
compromising C5/C5b activity is a useful strategy for developing an effective vaccine for antibody mediated and C5a
dependent inflammatory diseases. Further developing of
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