SARS-CoV-2 vaccine research and development: Conventional vaccines and biomimetic nanotechnology strategies

Abstract

The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is essential for stopping the current coronavirus disease (COVID-19) pandemic. A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection. Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) since the outbreaks of these diseases. The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses. In this review, we present the status of the development of coronavirus vaccines, focusing particularly on the biomimetic nanoparticle technology platform, which is likely to have a major role in future developments of personalized medicine.

Keywords: Biomimetic nanotechnology; COVID-19; SARS-CoV-2; Vaccine; Virus-like nanoparticles.

Graphical abstract

Fig. 1

Immune response to an Ad vector vaccine. When the Ad vector vaccine infects non-APCs, the infected cells express and secrete antigenic proteins, which are taken by antigen-presenting cells (APCs) and B cells. The antigenic proteins are degraded into antigenic peptides. APCs present exogenous antigenic peptides to CD4⁺ T cells through MHC-II. Cytokines produced by activated CD4⁺ T cells contribute to the activation of CD8⁺ T cells. B cells present antigenic peptides to follicular T helper cells through MHC-II, thereby promoting further B cell differentiation into long-lived antibody-producing plasma cells. When the Ad vector vaccine infects APCs, the vaccine expresses the antigen protein which is subsequently digested into antigenic peptides. The antigenic peptides are then presented to CD8⁺ T cells through MHC-I. In this way, both T cell subsets are activated.

Fig. 2

mRNA vaccine-mediated antigen presentation via MHC-I and MHC-II pathways. When an mRNA vaccine is taken by APCs, the antigenic proteins are translated in these cells. These proteins become endogenous proteins and are degraded by the proteasome into small peptides. The peptides are transported to the endoplasmic reticulum and loaded onto MHC-I molecules, and then activate CD8⁺ T cells through the MHC-I pathway. In the endoplasmic reticulum, MHC-II molecules are protected by an invariant chain (Ii) to prevent them from binding to endogenous peptides. The MHC-II-Ii complex is exported to the fusion vesicle through the Golgi apparatus, and then the invariant chain is replaced by exogenous antigenic peptides. When the vaccine is taken by non-APC cells, it will express and secreted antigenic proteins. These exogenous proteins enter APCs through endocytosis and activate CD4⁺ T cells through the MHC-II pathway.

Fig. 3

Generation of SARS-CoV-2 CpG-VLPs vaccine and the corresponding immune response. VLPs induce humoral immunity through the B cells and cross-presentation. VLPs induce cellular immunity through antigen-presenting cells.