期刊
EXPERT REVIEW OF VACCINES
卷 15, 期 8, 页码 1041-1053出版社
TAYLOR & FRANCIS LTD
DOI: 10.1586/14760584.2016.1159135
关键词
Ply-N-acetyl glucosamine; conjugate vaccine; capsule; antibiotic-resistance; monoclonal antibody
类别
资金
- Brigham and Women's Hospital from Alopexx Pharmaceuticals, LLC
- Alopexx Vaccine, LLC.
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-beta-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.
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