von Loga, Isabell S; El-Turabi, Aadil; Jostins, Luke; Miotla-Zarebska, Jadwiga; Mackay-Alderson, Jennifer; Zeltins, Andris; Parisi, Ida; Bachmann, Martin F.; Vincent, Tonia L (2019). Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis. Annals of the rheumatic diseases, 78(5), pp. 672-675. BMJ Publishing Group 10.1136/annrheumdis-2018-214489
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OBJECTIVES
Nerve growth factor (NGF) has emerged as a key driver of pain in osteoarthritis (OA) and antibodies to NGF are potent analgesics in human disease. Here, we validate a novel vaccine strategy to generate anti-NGF antibodies for reversal of pain behaviour in a surgical model of OA.
METHODS
Virus-like particles were derived from the cucumber mosaic virus (CuMV) and coupled to expressed recombinant NGF to create the vaccine. 10-week-old male mice underwent partial meniscectomy to induce OA or sham-surgery. Spontaneous pain behaviour was measured by Linton incapacitance and OA severity was quantified using OARSI histological scoring. Mice (experimental and a sentinel cohort) were inoculated with CuMVttNGF (Vax) or CuMVttctrl (Mock) either before surgery or once pain was established. Efficacy of anti-NGF from the plasma of sentinel vaccinated mice was measured in vitro using a neurite outgrowth assay in PC12 cells.
RESULTS
Anti-NGF titres were readily detectable in the vaccinated but not mock vaccinated mice. Regular boosting with fresh vaccine was required to maintain anti-NGF titres as measured in the sentinel cohort. Both prophylactic and therapeutic vaccination demonstrated a reversal of pain behaviour by incapacitance testing, and a meta-analysis of the two studies showing analgesia at peak anti-NGF titres was highly statistically significant. Serum anti-NGF was able to inhibit neurite outgrowth equivalent to around 150 ug/mL of recombinant monoclonal antibody.
CONCLUSIONS
This study demonstrates therapeutic efficacy of a novel NGF vaccine strategy that reversibly alleviates spontaneous pain behaviour in surgically induced murine OA.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology |
UniBE Contributor: |
Bachmann, Martin (B) |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0003-4967 |
Publisher: |
BMJ Publishing Group |
Language: |
English |
Submitter: |
Lee-Anne Brand |
Date Deposited: |
18 Nov 2019 10:41 |
Last Modified: |
29 Mar 2023 23:36 |
Publisher DOI: |
10.1136/annrheumdis-2018-214489 |
PubMed ID: |
30862648 |
Uncontrolled Keywords: |
chronic pain immunization nerve growth factor osteoarthritis vaccine |
BORIS DOI: |
10.7892/boris.135092 |
URI: |
https://boris.unibe.ch/id/eprint/135092 |
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