Bivalent mucosal peptide vaccines administered using the LCP carrier system stimulate protective immune responses against Streptococcus pyogenes infection

Nanomedicine. 2017 Nov;13(8):2463-2474. doi: 10.1016/j.nano.2017.08.015. Epub 2017 Sep 5.

Abstract

Despite the broad knowledge about the pathogenicity of Streptococcus pyogenes there is still a controversy about the correlate of protection in GAS infections. We aimed in further improving the immune responses stimulated against GAS comparing different vaccine formulations including bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) and BPPCysMPEG, a derivative of the macrophage-activating lipopeptide (MALP-2), as adjuvants, respectively, to be administered with and without the universal T helper cell epitope P25 along with the optimized B cell epitope J14 of the M protein and B and T cell epitopes of SfbI. Lipopeptide based nano carrier systems (LCP) were used for efficient antigen delivery across the mucosal barrier. The stimulated immune responses were efficient in protecting mice against a respiratory challenge with a lethal dose of a heterologous S. pyogenes strain. Moreover, combination of the LCP based peptide vaccine with c-di-AMP allowed reduction of antigen dose at the same time maintaining vaccine efficacy.

Keywords: Lipid core peptide system; Lipopeptides; Mucosal adjuvants; Peptide-based vaccines; Streptococcus pyogenes.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / therapeutic use*
  • Administration, Intranasal
  • Animals
  • Antibody Formation
  • Dinucleoside Phosphates / administration & dosage
  • Dinucleoside Phosphates / therapeutic use
  • Epitopes / administration & dosage
  • Epitopes / therapeutic use
  • Female
  • Lipopeptides / administration & dosage
  • Lipopeptides / therapeutic use
  • Mice, Inbred BALB C
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use
  • Streptococcal Infections / immunology
  • Streptococcal Infections / prevention & control*
  • Streptococcal Vaccines / administration & dosage
  • Streptococcal Vaccines / therapeutic use*
  • Streptococcus pyogenes / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / therapeutic use*

Substances

  • Adjuvants, Immunologic
  • Dinucleoside Phosphates
  • Epitopes
  • Lipopeptides
  • S-(2,3-bispalmitoyloxypropyl)-cysteinyl-amido-monomethoxyl polyethylene glycol
  • Streptococcal Vaccines
  • Vaccines, Subunit
  • cyclic diadenosine phosphate
  • Polyethylene Glycols
  • macrophage stimulatory lipopeptide 2