The exceptionally broad-based potential of active and passive vaccination targeting the conserved microbial surface polysaccharide PNAG

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
• conjugate vaccine
• capsule
• antibiotic-resistance
• monoclonal antibody

Financial and competing interests disclosure

GB Pier is an inventor of intellectual properties [human monoclonal antibody to PNAG and PNAG vaccines] that are licensed by Brigham and Women’s Hospital to Alopexx Vaccine, LLC, and Alopexx Pharmaceuticals, LLC, entities in which GB Pier also holds equity. As an inventor of intellectual properties, GB Pier also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Pharmaceuticals, LLC, and Alopexx Vaccine, LLC. GB Pier’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Partners Healthcare in accordance with their conflict of interest policies. D Skurnik and C Cywes-Bentley are inventors of intellectual properties [use of human monoclonal antibody to PNAG and use of PNAG vaccines] that are licensed by Brigham and Women’s Hospital to Alopexx Vaccine, LLC, and Alopexx Pharmaceuticals, LLC. As inventors of intellectual properties, C Cywes-Bentley and D Skurnik also have the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Pharmaceuticals, LLC, and Alopexx Vaccine, LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.