Biologic antibody therapeutics that target nerve growth factor (NGF) can alleviate osteoarthritis (OA) pain, but would probably be expensive to use clinically. Furthermore, concerns exist that this pain relief method might not be a lasting treatment as a result of the emergence of anti-drug antibodies. New research using the destabilization of the medial meniscus (DMM) model of OA now shows that vaccinating against NGF might be a suitable alternative.

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“This work was very much a collaborative project,” says Tonia Vincent, corresponding author of the study. “Martin Bachmann’s group was engineering a vaccine that would induce mice to make antibodies to their own NGF and meanwhile we were working out how to measure spontaneous pain behaviour in mouse models of knee OA.”

Bachmann (who is also a corresponding author on the study) and his group created the vaccine by covalently linking recombinant NGF with a virus-like particle derived from the cucumber mosaic virus.

“It is possible to hoodwink the immune system to making ‘self’ antibodies by dressing up the antigen on these viral particles,” explains Vincent. “This creates a polyclonal antibody response that can be tuned by the interval of further vaccine boosts. As these vaccines do not break tolerance, endogenous NGF is unable to stimulate an antibody response in the absence of the decorated viral particle.”

Vincent’s group injected this NGF vaccine into mice either before DMM or 10 weeks after DMM plus regular booster injections. Incapacitance testing was then used to assess how the mice distributed their body weight between the destabilized and control limbs. Asymmetrical weight distribution in DMM mice was reversed by vaccination, indicating a reduction in pain experienced by these mice.

Asymmetrical weight distribution in DMM mice was reversed by vaccination

“In the next phase we will test how effective the vaccine is in a veterinary setting by treating OA pain in companion animals,” says Bachmann. “Animals such as dogs and horses naturally develop OA, so this vaccine could benefit them and showing this treatment works in these animals might support a move to clinical trials in patients with OA.”