Physical mixture of a cyclic lipopeptide vaccine induced high titres of opsonic IgG antibodies against group A streptococcus

Biomater Sci. 2021 Dec 21;10(1):281-293. doi: 10.1039/d1bm01333e.

Abstract

Untreated or reoccurring group A Streptococcus (GAS) infection can lead to a number of post-infection complications, including rheumatic heart disease. There is no licenced vaccine for the treatment or prevention of GAS infection. We identified that a cyclic decapeptide plays a significant positive influence on the adjuvant activity of several lipid-antigen mixtures. Here, three synthetic vaccine components were synthesised: (1) J8-PADRE represents the GAS B cell antigen (J8) conjugated to the universal T helper epitope (PADRE); (2) a synthetic toll like receptor 2 (TLR2) ligand based on a C16 alkyl chain lipid moiety; and (3) a cyclic carrier deca-peptide. Previously, through structure-immune activity investigations, it was observed that a physical mixture of these three components had significantly higher IgG immune responses when compared to a fully conjugated vaccine construct. Expanding the scope of this structure-activity investigation, we show that the presence of the cyclic peptide is required for the induction of a strong, balanced Th1/Th2 immune response when compared with lipid and antigen only, and cyclic lipopeptide plus B/T cell antigen physical mixtures.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Bacterial / blood
  • Female
  • HEK293 Cells
  • Humans
  • Immunoglobulin G* / blood
  • Lipopeptides
  • Mice
  • Mice, Inbred C57BL
  • Peptides, Cyclic*
  • Streptococcal Infections / prevention & control*
  • Streptococcus pyogenes
  • Vaccines*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Immunoglobulin G
  • Lipopeptides
  • Peptides, Cyclic
  • Vaccines