Development of multi-epitope peptide-based vaccines against SARS-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic involving so far more than 15 million infections and 630,211 deaths. Effective vaccines are urgently needed to prevent SARS-CoV-2 infections. No vaccines have yet been approved for licensure by regulatory agencies. Even though host immune responses to SARS-CoV-2 infections are beginning to be unravelled, effective clearance of virus will depend on both humoral and cellular immunity. Additionally, the presence of Spike (S)-glycoprotein reactive CD4+ T-cells in the majority of convalescent patients is consistent with its significant role in stimulating B and CD8+ T-cells. The search for immunodominant epitopes relies on experimental evaluation of peptides representing the epitopes from overlapping peptide libraries which can be costly and labor-intensive. Recent advancements in B- and T-cell epitope predictions by bioinformatic analysis have led to epitope identifications. Assessing which peptide epitope can induce potent neutralizing antibodies and robust T-cell responses is a prerequisite for the selection of effective epitopes to be incorporated in peptide-based vaccines. This review discusses the roles of B- and T-cells in SARS-CoV-2 infections and experimental validations for the selection of B-, CD4+ and CD8+ T-cell epitopes which could lead to the construction of a multi-epitope peptide vaccine. Peptide-based vaccines are known for their low immunogenicity which could be overcome by incorporating immunostimulatory adjuvants and nanoparticles such as Poly Lactic-co-Glycolic Acid (PLGA) or chitosan.

Safety of COVID-19 vaccines administered in the EU: Should we be concerned?

“…These cells uptake LNPs and express the mRNA-encoded antigen which is further processed by the proteasome to generate peptide epitopes which are presented in the cell membrane. Subsequently, APC migrate to nearby draining lymph nodes where T-cell priming occurs [ 12 , 13 ]. Likewise, passive drainage of mRNA–LNPs through lymphatic vessels allows direct delivery of mRNA to the lymph nodes containing resident antigen-presenting cells and T-cells within them [ 14 ].…”

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

“…To select specific immunogenic epitopes and accelerate vaccine development, the SARS-CoV-2 genes were analyzed for B and T cell epitope candidates. In addition, the authors propose to increase the low immunogenicity of a peptide vaccine by including an adjuvant in its composition and using an effective delivery system based on chitosan or a copolymer of lactic and glycolic acid (PLGA) [ 291 ]. It is suggested that peptides derived from the short-palate, lung and nasal epithelial clone-1 (SPLUNC1), alpha-1-antitrypsin (AAT), dornase alfa (DA) and neutralizing human S230 light chain antibodies can be used as anti-adhesion agents, preventing the SARS-CoV-2 virus from interacting with the human host cell.…”

Various theranostics and immunization strategies based on nanotechnology against Covid-19 pandemic: An interdisciplinary view

“…Many nucleic acid based vaccines encode a whole genome or whole structural motifs. Encapsulating whole S-protein can trigger a broad spectrum of both humoral and cellular immune responses due to large repository of potent epitopes [ 250 ]. Previous vaccine development projects against SARS and MARS group of coronavirus; widely experienced similar prejudices from antibody dependent infection enhancement and that can cause life threatening allergic infection due to establishment of non-neutralizing antibody pool, which gradually increases infection [ 251 ].…”