Protein-Based Nanoparticle Vaccines for SARS-CoV-2.

Hyo-Dong Sung,Eun Jung Lee,Nayeon Kim,Yeram Lee

doi:10.3390/ijms222413445

Abstract

The pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has upended healthcare systems and economies around the world. Rapid understanding of the structural biology and pathogenesis of SARS-CoV-2 has allowed the development of emergency use or FDA-approved vaccines and various candidate vaccines. Among the recently developed SARS-CoV-2 candidate vaccines, natural protein-based nanoparticles well suited for multivalent antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses are currently being investigated. This mini-review presents recent innovations in protein-based nanoparticle vaccines against SARS-CoV-2. The design and strategy of displaying antigenic domains, including spike protein, receptor-binding domain (RBD), and other domains on the surface of various protein-based nanoparticles and the performance of the developed nanoparticle-based vaccines are highlighted. In the final part of this review, we summarize and discuss recent advances in clinical trials and provide an outlook on protein-based nanoparticle vaccines.

Highlights

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which first appeared in Wuhan, People’s Republic of China, in late 2019 and has since spread around the world, resulting in a pandemic [1,2]
This review mainly focuses on recent innovations in protein-based nanoparticle vaccines for protection against SARS-CoV-2 (Figure 1)
The design and strategy of displaying antigenic domains, including S protein, receptor-binding domain (RBD), and other domains, into various protein nanoparticles are discussed. The performance of these engineered protein nanoparticle vaccines for protection against SARS-CoV-2 in mice, human angiotensin-converting enzyme 2 (ACE2) transgenic mice, rabbits, hamsters, ferrets, and macaques, and their ability to protect against other viruses in the Coronaviridae family is highlighted

Summary

Introduction

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which first appeared in Wuhan, People’s Republic of China, in late 2019 and has since spread around the world, resulting in a pandemic [1,2]. Ferritin-based protein nanoparticles presenting the SARS-CoV-2 S protein are entering phase 1 clinical trials (NCT04784767). These nanoparticle-based vaccine technologies can enhance the immunogenicity and stability of soluble antigens by multivalent antigen display on their surface [17,18,19,20,21,22,23]. The design and strategy of displaying antigenic domains, including S protein, receptor-binding domain (RBD), and other domains, into various protein nanoparticles are discussed The performance of these engineered protein nanoparticle vaccines for protection against SARS-CoV-2 in mice, human angiotensin-converting enzyme 2 (ACE2) transgenic mice, rabbits, hamsters, ferrets, and macaques, and their ability to protect against other viruses in the Coronaviridae family is highlighted. The S protein-displaying nanoparticles with QuilA/monophosphoryl lipid A successfully elicited a more consistent neutralizing antibody response compared with that with a trimeric form of S protein using the trimeric coiled-coil protein GCN4 and higher S-pseudotyped viral neutralizing titers than those in convalescent COVID-19 patient plasma, even in a single dose

AddaVax or Sigma Adjuvant

Findings

Conclusions and Perspectives