A novel nanoparticle-based vaccine against SARS-CoV-2 assembled on a nanomimetic amyloid for controlled antigen release

Abstract

The COVID-19 pandemic has been an unprecedented situation regarding its fast spread and the associated economical losses. Since late 2019 when it first emerged, SARS-CoV-2 has already caused millions of deaths worldwide and despite vaccination efforts continues to escalate. Even though several vaccines are already commercially available, they still face several limitations that open space for the development of smarter and safer alternatives. Here we propose the use of two technologies combined to achieve improved vaccine formulations against SARS-CoV-2. First, we will employ self-assembling protein nanoparticles (SAPN) to promote the assembly of spike and parts thereof in 3-dimensional multimeric structures that mimic pathogen-associated molecular patterns and boost humoral responses. Second, these so-called nanovaccines will be further chemically modified by the addition of divalent cations to induce the formation of functional amyloids that act as secreting granules. These materials, acting as depots, will allow a controlled release of nanoscale antigens in vivo. The production of both SAPN and amyloids will be optimized and characterized regarding size and morphology, and the released nanostructured antigens will also be monitored and assessed. The secreting granules will be administered subcutaneously in BALB/c mice in a prime/boost vaccination regimen and sera will be collected to evaluate humoral responses. The antibodies elicited are expected to have a strong virus neutralizing capacity in vitro and to confer protection on a lethal challenge of vaccinated susceptible ACE-2-expressing mice. This project poses the opportunity not only to develop an efficient vaccine formulation against SARS-CoV-2, but also to further develop and fine-tune nanovaccine formulations that could be applied to any infectious disease. (AU)