Lipopeptides for Vaccine Development.

ABSTRACT

The development of lipopeptides (lipidated peptides) for vaccines is discussed, including their role as antigens and/or adjuvants. Distinct classes of lipopeptide architectures are covered including simple linear and ligated constructs and lipid core peptides. The design, synthesis, and immunological responses of the important class of glycerol-based Toll-like receptor agonist lipopeptides such as Pam3CSK4, which contains three palmitoyl chains and a CSK4 hexapeptide sequence, and many derivatives of this model immunogenic compound are also reviewed. Self-assembled lipopeptide structures including spherical and worm-like micelles that have been shown to act as vaccine agents are also described. The work discussed includes examples of lipopeptides developed with model antigens, as well as for immunotherapies to treat many infectious diseases including malaria, influenza, hepatitis, COVID-19, and many others, as well as cancer immunotherapies. Some of these have proceeded to clinical development. The research discussed highlights the huge potential of, and diversity of roles for, lipopeptides in contemporary and future vaccine development.