Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis. Issue 5 (11th May 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Annals of the rheumatic diseases. Volume 78:Issue 5(2019)
• Page Start: 672
• Publication Date: 2019-05-11
• Subjects: immunization -- vaccine -- osteoarthritis -- chronic pain -- nerve growth factor; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-214489
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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 CuMVtt NGF (Vax) or CuMVtt ctrl (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.