Spike-NanoGhost as a safe and potent immunization platform against COVID-19

Since its outbreak, the Covid-19 pandemic has infected around 185 million people, leading to more than 4 million deaths worldwide within a year and a half. Like other coronavirus strains, the new SARS-CoV-2 coronavirus - identified as the cause of Covid-19 - is characterized by a spherical morphology with four structural proteins – envelope, membrane, nucleocapsid, and spike (S) proteins. The last was suggested as a key target because of its part in viral attachment, fusion, and entry. Great efforts have been made to develop approaches against the virus including the development of virus inhibitors, neutralizing antibodies, and most importantly - vaccines, which are the most efficient and cost-effective means to prevent and control COVID-191. Nevertheless, the development of a vaccine faces major challenges, primarily achieving the right level of immunogenicity, antigen presentation, adjuvant addition, and potent antibody stimulation.

Here, we propose a unique approach that relies on the presentation of viral S protein on vesicles prepared from the cytoplasmatic membranes of mammalian stem cells and called NanoGhosts (NGs)2. These vesicles are equipped with the means to ensure maximal safety and fully protective immunization through a non-viral inanimate platform. NGs were originally developed as a targeted delivery system for tumors3 and inflammation sites by exhibiting molecules on their external surface that characterize the original cell membrane, or altered through engineering the original cells. The knowledge accumulated in our lab in the last decade had revealed their exceptional potential as a safe platform for antigen presentation in a novel vaccine delivery platform. Using human mesenchymal stem cells (hMSCs)-derived NGs has advantages such as inherent interactions with cells of the immune system, but it also holds risks such as reduced immunization and, most importantly, immunization against self-hMSC antigens. These risks and advantages are thoroughly addressed in the current research using MSCs and BHK cells that were engineered to express spike proteins on their membrane and to retain the proteins on the NGs produced from those cells. NGs produced from these engineered cells are tested for their interaction of Spikes-NGs (SNGs) with antigen-presenting cells in vitro and with the aim to evaluate the vaccine efficacy and safety in vivo.