Figure 12. String-of-beads vaccines (SBVs) for multi-epitope delivery.

A. The concept of SBVs for infectious disease agents (e.g., influenza and cytomegalovirus) is based on expressing multiple epitopes from pathogen antigens separated by cleavable spacers.¹¹⁰ It is envisaged that the design tools for the selection of multiple epitopes and their encapsulation in suitable nanocarriers will facilitate SARS-CoV-2 epitope delivery to regional lymph nodes, where individual epitopes will be released by proteolytic processing and presented by dendritic cells. Vaccine efficiency would depend on the optimal combination of B and T-cell epitopes as well as the use of appropriate spacers to allow efficient epitope release.¹¹⁰ Reprinted with permission from ref 110 under the Creative Commons Attribution 4.0 International License. Copyright 2016 Springer Nature. B. Multi-epitope vaccines have received a boost from new immunoinformatic tools for vaccine design, using a series prediction tools as outlined in Table 3. In this example, Yarmarkovich et al. report the design of multi-epitope vaccines that deliver 65 x 33-mer SARS-CoV-2 peptides, making use of the following guidelines: (i) selection of peptide sequences from 15 related coronaviruses; (ii) epitope ability to activate CD4⁺ and CD8⁺ T-cells by enabling interactions with diverse HLA gene sequences; (iii) B-cell activation by linear and conformational epitope sequences; (iv) high immunogenicity through sequence selection that is significantly dissimilar to the self-proteome; (v) vaccine safety.¹⁰⁹ Reprinted with permission from ref 109 under the Creative Commons License CC-BY 4.0. Copyright 2020 The Authors.