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Jun 13, 2013
 |  BC Innovations  |  Targets & Mechanisms

PNAG: broadening infection protection

A multi-institutional team has added more than 20 pathogens to the list of known bacteria that express poly-N-acetylglucosamine, a bacterial capsule polysaccharide that provides a potentially broad-spectrum target for vaccination.1 The findings open up new indications for Alopexx Vaccine LLC and Alopexx Pharmaceuticals LLC, which are already developing a vaccine and an antibody for passive immunization, respectively.

Over the past two decades, studies by multiple groups have identified poly-N-acetylglucosamine (PNAG), a polysaccharide encoded by a conserved four-gene locus, as a component of the surface capsule in at least seven species of bacteria.2-7

PNAG is one of many polysaccharides and other carbohydrate polymers found on the outer surface of bacteria that help prevent host macrophages and other cells from engulfing the pathogens.

Anti-PNAG antibodies have been found in circulation in humans and other animals, but these naturally occurring antibodies do not effectively kill PNAG-expressing bacteria or provide adequate immune protection against them, casting doubts on their prophylactic potential.8-10

Between 2005 and 2007, teams led by Gerald Pier showed that a deacetylated form of PNAG (dPNAG) elicited bacteria-killing antibodies in mice.6,11 His teams also developed a human mAb-dubbed F598-that bound to both dPNAG and PNAG and killed bacteria.12

Pier is professor of medicine in microbiology and immunology at Harvard Medical School and a microbiologist in the department of medicine at Brigham and Women's Hospital.

In the current study, Pier's team investigated whether PNAG was expressed on bacteria and other pathogens in which the four-gene PNAG-producing locus has not yet been identified.

The group used F598 conjugated to a fluorescent agent to detect PNAG on the surfaces of pathogens and found the molecule in 24 pathogens not previously known to express it. Among the new pathogens were disease-causing bacteria such as Streptococcus pneumoniae, Clostridium difficile and Mycobacterium tuberculosis, as well as the yeast Candida albicansand the parasite Plasmodium falciparum (see "Adding pathogens to the PNAG list")

In human cell-based bactericidal assays, F598 increased killing of C. albicans, Neisseria meningitidis, S. pneumoniae and other pathogens compared with an inactive control antibody.

Lastly, the team tested the protective effect...

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