A Unique Protein Self-Assembling Nanoparticle with Significant Advantages in Vaccine Development and Production

Abstract

Nanoparticles are playing an increasingly powerful role in vaccine development. Here, we report the repurposing of nonstructural proteins 10 and 11 (hereafter NSP10) from the replicase polyprotein 1a (pp1a) of the human SARS coronavirus (severe acute respiratory syndrome) as a novel self-assembling platform for bioengineered nanoparticles for a variety of applications including vaccines. NSP10 represents a 152 amino acid, 17 kD zinc finger transcription/regulatory protein which self-assembles to form a spherical 84 Å diameter nanoparticle with dodecahedral trigonal 32 point symmetry. As a self-assembling nanoparticle, NSP10 possesses numerous advantages in vaccine development and antigen display, including the unusual particle surface disposition of both the N- and C-termini. Each set of N- or C-termini is spatially disposed in a tetrahedral arrangement and positioned at optimal distances from the 3-fold axes (8-10 Å) to nucleate and stabilize the correct folding of complex helical or fibrous trimeric receptors, such as those responsible for viral tropism and cell infection. An application example in the exploratory development of a therapeutic vaccine for idiopathic pulmonary fibrosis (IPF), including preliminary analysis and immunogenic properties, is presented. The use of this system could accelerate the discovery and development of vaccines for a number of human, livestock, and veterinary applications.

Nanoparticle-Based Strategies to Combat COVID-19

“…The poly(I:C) adjuvant is able to activate a relatively high number of DCs in lymph nodes to generate a robust immune response. Cross-virus VLP design was also studied by Carter et al 132 SARS-CoV polyprotein 1a (pp1a) self-assembled into VLPs that were found to be effective against idiopathic pulmonary fibrosis (IPF) caused by Herpesvirus saimiri (HVS). These two studies show that VLPs developed using subunits from one virus can serve as effective vaccines against other viruses as well.…”

On Facing the SARS-CoV-2 (COVID-19) with Combination of Nanomaterials and Medicine: Possible Strategies and First Challenges

“…Poly (lactic-co-glycolic acid) (PLGA) is one of the well-known member of this category which is approved by FDA for application in human body. This is due to the excellent biocompatibility and biodegradability in the human body [94]. Other examples include chitosan, and N-(2-hydroxypropyl) methacrylamide/N-isopropylacrylamide (HPMA/NIPAM) which showed promising results as intranasal vaccines against respiratory viruses Self-assembling proteins NPs: These are prepared through the oligomerization of monomeric proteins, which were found suitable for biomedical applications [95].…”

Self-assembled Viral Nanoparticles as Targeted Anticancer Vehicles

“…A most recent example was the repurposing of nonstructural protein 10 (NSP10) from the replicase polyprotein 1a of human severe acute respiratory syndrome (SARS) coronavirus to exploit a selfassembling platform for antigen presentation and vaccine development, e.g. the truncated Herpesvirus saimiri gD protein fusion-expressed with NSP10 as a therapeutic vaccine for idiopathic pulmonary fibrosis [140]. Viruses have been proven as useful development platform for novel vaccines because of their particulate and repetitive nature.…”