Self-Assembling Protein Nanoparticles in the Design of Vaccines: 2022 Update

Abstract

Vaccines constitute a pillar in the prevention of infectious diseases. The unprecedented emergence of novel immunization strategies due to the COVID-19 pandemic has again positioned vaccination as a pivotal measure to protect humankind and reduce the clinical impact and socioeconomic burden worldwide. Vaccination pursues the ultimate goal of eliciting a protective response in immunized individuals. To achieve this, immunogens must be efficiently delivered to prime the immune system and produce robust protection. Given their safety, immunogenicity, and flexibility to display varied and native epitopes, self-assembling protein nanoparticles represent one of the most promising immunogen delivery platforms. Currently marketed vaccines against the human papillomavirus, for instance, illustrate the potential of these nanoassemblies. This review is intended to provide novelties, since 2015, on the ground of vaccine design and self-assembling protein nanoparticles, as well as a comparison with the current emergence of mRNA-based vaccines.

Keywords: SAPNs; VLPs; antibodies; antigen; foot and mouth disease (HFMD); hand; human papillomavirus (HPV); immunogen; nanoparticles; norovirus (NoV); self-assembling protein nanoparticles; vaccine; virus; virus-like particles.

Figure 1

Chronology of vaccine development in the context of self-assembling protein nanoparticles. The milestones achieved by vaccinologists since 1982 are indicated. Figure created in BioRender. Abbreviations: hepatitis B virus (HBV), human papillomavirus (HPV) and hepatitis E virus (HEV).

Figure 2

Viral- and vaccine-elicited immune reactions. The figure shows a schematic comparison of the differences and similarities regarding the elicitation of an immune response by live viruses, SAPNs, or DNA/RNA vaccines. Host immune reactions follow common pathways, regardless of whether the trigger is a natural pathogen or vaccine formulation. The main difference among these pathways is that in vaccine-elicited reactions antigen that is delivered to the host, as in the case of recombinant proteins or SAPNs, directly initiates an immune response by activating antigen-presenting cells (APCs). On the contrary, mRNA- or adenovirus-based vaccines require a prior step whereby host target cells will produce the desired immunogen. APCs fragment the immunogen into smaller peptides and present them on their surface-by-surface receptors to several types of cells in the host, such as cytotoxic (CD8⁺) T, helper (CD4⁺) T and B cells. B cells are activated by immunogen recognition, differentiate into plasma cells, and secrete antibodies that neutralize the virus. The activation of CD4⁺ T cells by APCs causes them to differentiate into different subtypes, such as T follicular helper cells (T_FH), which also help B cells to differentiate into memory B cells and antibody-secreting plasma cells and promote the production of high-affinity antibodies. Another subset of CD4⁺ T cells differentiates into memory T helper cells. Cytotoxic T cells activation by APCs interaction cause apoptosis by cytotoxic mediators release to the host cells that are infected with the virus. Some CD8⁺ T cells differentiate into memory cytotoxic T cells, which show a fast response against secondary immunogen contact. Figure created in BioRender. PFN: perforin; GzmB: Granzyme B; IFNγ: Interferon γ; TNFα: Tumor necrosis factor α.

Figure 3

Structure and location of the DE loop in the HPV SAPN particle. The capsid of the type 16 HPV is shown in the left panel, as a surface-coloured representation. The pentamer formed by the L1 protein is displayed in a zoomed-in image in the centre panel, with each of the L1 monomers shown in individual colours in cartoon mode. The DE loop is highlighted in red colour. The right panel shows an individual L1 protein (monomer).

Figure 4

Structural flexibility in the design of SAPNs. Schematic view of three different designs of SAPNs with the core self-assembling proteins, and immunogenic epitopes mounted for surface display. Figures created in BioRender.