Synthesis and Evaluation of a QS-17/18-Based Vaccine Adjuvant

J Med Chem. 2019 Feb 14;62(3):1669-1676. doi: 10.1021/acs.jmedchem.8b01997. Epub 2019 Jan 18.

Abstract

We have synthesized a QS-17/18 analogue (7) and evaluated its adjuvant activity in the formulation with rHagB antigen. Compound 7 and QS-21 analogues 5 and 6 are presumably the major components of GPI-0100, a widely used complex mixture of semisynthetic derivatives of Quillaja saponaria (QS) Molina saponins. The QS-17/18 analogue 7 shows an adjuvant activity profile similar to that of GPI-0100, potentiating mixed Th-1/Th-2 immune responses, which is different from those of QS-21 analogues 5 and 6 that probably only induce a Th2-like immunity. The combination of QS-17/18 and QS-21 analogues does not show a synergistic effect. These results suggest that QS-17/18 analogue 7 might be the active component of GPI-0100 responsible for its immunostimulant property. Therefore, compound 7 can not only be a structurally defined alternative to GPI-0100 but also provide a valuable clue for rational design of new QS-based vaccine adjuvants with better adjuvant properties.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adhesins, Bacterial / immunology
  • Adjuvants, Immunologic / chemical synthesis
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Female
  • Immunoglobulin G / metabolism
  • Lectins / immunology
  • Mice, Inbred BALB C
  • Recombinant Proteins / immunology
  • Saponins / chemical synthesis
  • Saponins / immunology
  • Saponins / pharmacology*
  • Th1 Cells / drug effects
  • Th2 Cells / drug effects

Substances

  • Adhesins, Bacterial
  • Adjuvants, Immunologic
  • GPI0100
  • HagB protein, Porphyromonas gingivalis
  • Immunoglobulin G
  • Lectins
  • Recombinant Proteins
  • Saponins