The use of a gold nanoparticle-based adjuvant to improve the therapeutic efficacy of hNgR-Fc protein immunization in spinal cord-injured rats

As a common receptor for three myelin associated inhibitors, Nogo-66 receptor (NgR) mediates their inhibitory activities on neurite outgrowth in the adult mammalian central nervous system (CNS). Therapeutic vaccination protocol targeting NgR emulsified with Freund's adjuvant (FA) has been used in spinal cord injury (SCI) models. However, the vaccine emulsified with FA may induce some side effects, which are not suitable for further clinical application. As an adjuvant, gold nanoparticles (GNPs) could stimulate a stronger immune response without producing detectable toxicity and physiological damage than FA. There is, however, uncertainty regarding the efficacy of axon regeneration and neuroprotection in vaccines with GNPs as an adjuvant. In this investigation, a recombinant protein vaccine targeting NgR, human NgR-Fc (hNgR-Fc) fusion protein conjugated with 15 nm GNPs was prepared and its effects on axonal regeneration and functional recovery in spinal cord-injured rats were investigated. The results showed that adult rats immunized with the protein vaccine produced higher titers of anti-NgR antibody than that with FA, and the antisera promoted neurite outgrowth in presence of MAC in vitro. In a spinal cord dorsal hemisection model, vaccine immunized with GNPs promoted axonal regeneration more effectively than FA, resulted in significant protection from neuronal loss, and improved functional recovery. Thus, as an adjuvant, 15 nm GNPs can effectively boost the immunogenicity of hNgR-Fc protein vaccine, and promote the repair of spinal cord-injured rats. The utilization of GNPs, for clinical considerations, may be a more beneficial supplement than FA to the promising therapeutic vaccination strategy for promoting SCI repair. (C) 2011 Elsevier Ltd. All rights reserved.