Volume 60, November 2022, 108029Highlights•

Many highly potent vaccines have been designed based on chemical conjugation technology to fight a large variety of pathogens.

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The vaccine chemical structure modifications, for example, change of components' position, affect the vaccine efficacy.

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The number and type of lipids have significant influnce on lipopeptide vaccine immunological properties.

Abstract

Peptide-based subunit vaccines utilise minimal immunogenic components (i.e. peptides) to generate highly specific immune responses, without triggering adverse reactions. However, strong adjuvants and/or effective delivery systems must be incorporated into such vaccines, as peptide antigens cannot induce substantial immune responses on their own. Unfortunately, many adjuvants are too weak or too toxic to be used in combination with peptide antigens. These shortcomings have been addressed by the conjugation of peptide antigens with lipidic/ hydrophobic adjuvanting moieties. The conjugates have shown promising safety profiles and improved immunogenicity without the help of traditional adjuvants and have been efficient in inducing desired immune responses following various routes of administration, including subcutaneous, oral and intranasal. However, not only conjugation per se, but also component arrangement influences vaccine efficacy. This review highlights the importance of influence of the vaccine chemical structure modification on the immune responses generated. It discusses a variety of factors that affect the immunogenicity of peptide conjugates, including: i) self-adjuvanting moiety length and number; ii) the orientation of epitopes and self-adjuvanting moieties in the conjugate; iii) the presence of spacers between conjugated components; iv) multiepitopic arrangement; and v) the effect of chirality on vaccine efficacy.

Keywords

Self-adjuvanting peptides

Peptide design

Antigen structural modifications

Physicochemical properties

Immunostimulatory characteristics

Peptide-based vaccine efficacy

AbbreviationsAntigen-presenting cells

APCs

Complete Freund's adjuvant

CFA

Dipalmitoyl-S-glyceryl cysteine

Pam2Cys

Gonadotropin-releasing hormone

GnRH

Incomplete Freund's adjuvant

IFA

Influenza virus hemagglutinin

HA2

Major histocompatibility complex proteins

MHC

Multiple antigenic peptide system

MAP

Pan DR-biding epitope

PADRE

Pathogen-associated molecular patterns

PAMPs

Pattern recognition receptors

PRRs

Poly(hydrophobic amino acid)

pHAA

Solid-phase peptide synthesis

SPPS

Structure-activity relationships

SAR

T cell antigen receptors

TCRs

Tripalmitoyl-S-glyceryl cysteine

Pam3Cys

Tumour necrosis factor-α

TNF-α

α –galactosylceramide

α-GalCer

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© 2022 Published by Elsevier Inc.