Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis.

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)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Bachmann, Martin

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:

18 Nov 2019 10:41

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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