title: A virus-like particle-based anti-nerve growth factor vaccine reduces inflammatory hyperalgesia: potential long-term therapy for chronic pain.
abstract: Chronic pain resulting from inflammatory and neuropathic disorders causes considerable economic and social burden. For a substantial proportion of patients, conventional drug treatments do not provide adequate pain relief. Consequently, novel approaches to pain management, involving alternative targets and new therapeutic modalities compatible with chronic use, are being sought. Nerve growth factor (NGF) is a major mediator of chronic pain. Clinical testing of NGF antagonists is ongoing, and clinical proof of concept has been established with a neutralizing mAb. Active immunization, with the goal of inducing therapeutically effective neutralizing autoreactive Abs, is recognized as a potential treatment option for chronic diseases. We have sought to determine if such a strategy could be applied to chronic pain by targeting NGF with a virus-like particle (VLP)-based vaccine. A vaccine comprising recombinant murine NGF conjugated to VLPs from the bacteriophage Qβ (NGFQβ) was produced. Immunization of mice with NGFQβ induced anti-NGF-specific IgG Abs capable of neutralizing NGF. Titers could be sustained over 1 y by periodic immunization but declined in the absence of boosting. Vaccination with NGFQβ substantially reduced hyperalgesia in collagen-induced arthritis or postinjection of zymosan A, two models of inflammatory pain. Long-term NGFQβ immunization did not change sensory or sympathetic innervation patterns or induce cholinergic deficits in the forebrain, nor did it interfere with blood-brain barrier integrity. Thus, autovaccination targeting NGF using a VLP-based approach may represent a novel modality for the treatment of chronic pain.
authors.affiliation: Cytos Biotechnology AG, Immunodrugs, Zurich, Switzerland.
authors.forename: Till A
authors.initials: TA
authors.lastname: Röhn
authors.forename: William T
authors.initials: WT
authors.lastname: Ralvenius
authors.forename: Jolly
authors.initials: J
authors.lastname: Paul
authors.forename: Petra
authors.initials: P
authors.lastname: Borter
authors.forename: Marcela
authors.initials: M
authors.lastname: Hernandez
authors.forename: Robert
authors.initials: R
authors.lastname: Witschi
authors.forename: Paula
authors.initials: P
authors.lastname: Grest
authors.forename: Hanns Ulrich
authors.initials: HU
authors.lastname: Zeilhofer
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: Gary T
authors.initials: GT
authors.lastname: Jennings
mesh_terms: D000208:Acute Disease; D017908:Allolevivirus / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000502:physiology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002908:Chronic Disease; D004353:Drug Evaluation, Preclinical; D006930:Hyperalgesia / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009414:Nerve Growth Factors / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D009500:Neutralization Tests; D010146:Pain / Q000276:immunology* / Q000473:pathology; D059408:Pain Management; D051381:Rats; D013997:Time Factors; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D058425:Vaccines, Virus-Like Particle / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D000914:Antibodies, Viral; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D018074:Vaccines, Conjugate; D058425:Vaccines, Virus-Like Particle