Study of the adjuvanticity of lysine lipopeptides; carbamate analogs elicit strong Th1 and Th2 response to ovalbumin in mice

Int Immunopharmacol. 2011 Nov;11(11):1855-63. doi: 10.1016/j.intimp.2011.07.016. Epub 2011 Aug 30.

Abstract

Bacterial lipoproteins and their synthetic analogs are strong immune modulators of the early host responses. In view of the strong adjuvanticity of bacterial lipopeptide mimics bearing lysine residues, a focused library of lipidated dipeptides and tripeptides has been synthesized with a view to understand the pattern of activity vis a vis the site and extent of lipidation. Compounds 4, 5 and 14 stimulate OVA specific IgG titer, neutralization of antibodies (IgG1 and IgG2a), T lymphocyte sub-sets (CD4/CD8) and its production of soluble mediators for Th1 (IFN-γ)/Th2 (IL-4) cytokines and costimulatory molecules (CD80/CD86) which are ideal traits of immune adjuvants. The results support lipidated lysine dipeptides as potent enhancers of humoral and cell mediated immune responses and thus might become promising immune-adjuvants for self adjuvanted vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / chemical synthesis
  • Adjuvants, Immunologic* / chemistry
  • Adjuvants, Immunologic* / pharmacology
  • Animals
  • Antibodies, Neutralizing / blood
  • Antigens, CD / blood
  • Carbamates / chemical synthesis
  • Carbamates / chemistry
  • Carbamates / immunology*
  • Cell Proliferation / drug effects
  • Cytokines / blood
  • Cytokines / immunology
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunoglobulin G / blood
  • Immunophenotyping
  • Lipopeptides / chemical synthesis
  • Lipopeptides / chemistry
  • Lipopeptides / immunology*
  • Lysine / chemical synthesis
  • Lysine / chemistry
  • Lysine / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Ovalbumin / immunology
  • Solid-Phase Synthesis Techniques
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Vaccination / methods

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antigens, CD
  • Carbamates
  • Cytokines
  • Immunoglobulin G
  • Lipopeptides
  • Ovalbumin
  • Lysine