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

Abstract

Recombinant virus-like nanoparticles (VLPs) are a promising nanoparticle platform to develop safe vaccines for many viruses. Herein, we describe a novel and rapid protein transfer process to enhance the potency of enveloped VLPs by decorating influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs). With protein transfer, the level of GPI-ISM incorporation onto VLPs is controllable by varying incubation time and concentration of GPI-ISMs added. ISM incorporation was dependent upon the presence of a GPI-anchor and incorporated proteins were stable and functional for at least 4 weeks when stored at 4°C. Vaccinating mice with GPI-granulocyte macrophage colony-stimulating factor (GM-CSF)-incorporated-VLPs induced stronger antibody responses and better protection against a heterologous influenza virus challenge than unmodified VLPs. Thus, VLPs can be enriched with ISMs by protein transfer to increase the potency and breadth of the immune response, which has implications in developing effective nanoparticle-based vaccines against a broad spectrum of enveloped viruses.

Virus‐based nanoparticles as platform technologies for modern vaccines

“…FDA-approved treatments include the HER2-specific antibodies trastuzumab and pertuzumab, which are used for passive immunotherapy and require repetitive administration 162, 163 . Passive immunization requires prolonged therapeutic delivery, cannot be developed as a prophylactic, and does not induce cellular immune responses 77, 78 . To overcome these challenges, HER-2 + breast cancer research is now focused on active immunotherapy that elicits long-lasting cellular and humoral responses.…”

Progress in the development of virus-like particle vaccines against respiratory viruses

“…Using a protein transfer technology, glycosylphosphatidylinositolanchored immunostimulatory molecules (GPI-ISMs) are incorporated onto influenza VLPs [83]. Mice immunized with VLPs modified by protein transfer with GPI-GM-CSF induced higher levels of IgG antibody responses and protection against a heterologous influenza virus challenge than unmodified VLPs in mice [83]. Intranasal immunization with chimeric VLPs containing influenza HA antigen and GPI-CCL28 was shown to induce long-lasting mucosal immunity against H3N2 virus infection [84].…”

Progress in developing virus-like particle influenza vaccines

“…A recent study described a novel protein transfer technology to enhance the potency of enveloped VLPs by decorating influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored (GPI) granulocyte macrophage colony-stimulating factor (GM-CSF) [44]. Incorporation of immunostimulatory GM-CSF into influenza VLPs was dependent on the presence of GPI-anchor, and found to be stable and functional.…”