Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses

Virus-like nanoparticles (VLPs) are used as a platform to produce safe and effective vaccines against viruses, however cross-protection against heterologous viral strains is still difficult to obtain. Herein, we demonstrate a protein transfer method used to modify the surfaces of enveloped influenza VLPs to enhance the breadth and potency of influenza-specific immune responses. A simple incubation of VLPs with purified glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs) results in time and concentration-dependent incorporation of functional ISMs onto VLPs. Further, vaccination with GPI-GM-CSF-protein transferred-VLPs led to enhanced antiviral antibody responses and complete protection against heterologous influenza virus challenge unlike vaccination with unmodified VLPs.156