1. Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis
- Author
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von Loga, Isabell S, El-Turabi, Aadil, Jostins, Luke, Miotla-Zarebska, Jadwiga, Mackay-Alderson, Jennifer, Zeltins, Andris, Parisi, Ida, Bachmann, Martin F, and Vincent, Tonia L
- Subjects
Male ,Analgesics ,Vaccination ,Antibodies, Monoclonal ,610 Medicine & health ,immunization ,Disease Models, Animal ,Mice ,vaccine ,Osteoarthritis ,Nerve Growth Factor ,Pain Management ,Animals ,Chronic Pain - 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 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.
- Published
- 2019