Peptide-based synthetic vaccines

Abstract

Classically all vaccines were produced using live or attenuated microorganisms or parts of them. However, the use of whole organisms, their components or the biological process for vaccine production has several weaknesses. The presence of immunologically redundant biological components or biological impurities in such vaccines might cause major problems. All the disadvantageous of traditional vaccines might be overcome via the development of fully synthetic peptide-based vaccines. However, once minimal antigenic epitopes only are applied for immunisation, the immune responses are poor. The use of an adjuvant can overcome this obstacle; however, it may raise new glitches. Here we briefly summarise the current stand on peptide-based vaccines, discuss epitope and adjuvant design, and multi-epitope and nanoparticle-based vaccine approaches. This mini review discusses also the disadvantages and benefits associated with peptide-based vaccines. It proposes possible methods to overcome the weaknesses of the synthetic vaccine strategy and suggests future directions for its development.

Fig. 1. Schematic representation of major pathways of immune response.

Fig. 2. Peptide-based vaccines; pros, cons and solutions.

Fig. 3. Examples of an epitope modification to (a) stabilize conformation (and improve stability against enzymatic degradation) and (b) improve its stability in vivo.

Fig. 4. Examples of peptide-based vaccines and synthetic techniques used for their production: (a) lipid core peptide vaccine delivery system (produced by SPPS, occasionally with help of CuAAC); (b) vaccine produced with help of thioether ligation; (c) multicomponent vaccine obtained by polymerization/conjugation approach; (d) asymmetrical dendrimer produced with the help of copper-catalysed azide–alkyne cycloaddition; (e) multi-epitope construct produced by random polymerisation of several acrylate modified B-cell epitopes; (f) multiple different B-cell epitopes incorporated into one entity via stepwise SPPS using lysine-based branching; (g) recombinant polyepitope conjugated to adjuvanting moiety with the help of intein and native chemical ligation; (h) glycopeptide-based antigen synthesised in a mixed chemical/enzymatic approach.

Mariusz Skwarczynski

Istvan Toth