The Exceptionally Broad-Based Potential of Active and Passive Vaccination Targeting the Conserved Microbial Surface Polysaccharide PNAG

Expert Rev Vaccines. 2016 Aug;15(8):1041-53. doi: 10.1586/14760584.2016.1159135. Epub 2016 Mar 16.

Abstract

A challenging component of vaccine development is the large serologic diversity of protective antigens. Remarkably, there is a conserved surface/capsular polysaccharide, one of the most effective vaccine targets, expressed by a large number of bacterial, fungal and eukaryotic pathogens: poly-N-acetyl glucosamine (PNAG). Natural antibodies to PNAG are poorly effective at mediating in vitro microbial killing or in vivo protection. Removing most of the acetate substituents to produce a deacetylated glycoform, or using synthetic oligosaccharides of poly-β-1-6-linked glucosamine conjugated to carrier proteins, results in vaccines that elicit high levels of broad-based immunity. A fully human monoclonal antibody is highly active in laboratory and preclinical studies and has been successfully tested in a phase-I setting. Both the synthetic oligosaccharide conjugate vaccine and MAb will be further tested in humans starting in 2016; but, even if effective against only a fraction of the PNAG-producing pathogens, a major advance in vaccine-preventable diseases will occur.

Keywords: Ply-N-acetyl glucosamine; antibiotic-resistance; capsule; conjugate vaccine; monoclonal antibody.

Publication types

  • Review

MeSH terms

  • Acetylglucosamine / administration & dosage*
  • Acetylglucosamine / immunology*
  • Animals
  • Bacterial Vaccines / immunology*
  • Bacterial Vaccines / isolation & purification
  • Clinical Trials as Topic
  • Drug Discovery
  • Fungal Vaccines / immunology*
  • Fungal Vaccines / isolation & purification
  • Humans
  • Immunization, Passive / methods*
  • Malaria Vaccines / immunology*
  • Malaria Vaccines / isolation & purification
  • Vaccination / methods*

Substances

  • Bacterial Vaccines
  • Fungal Vaccines
  • Malaria Vaccines
  • poly-N-acetyl glucosamine
  • Acetylglucosamine