The influence of component structural arrangement on peptide vaccine immunogenicity

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.