Alopexx Vaccine, LLC was founded in 2010 to develop and commercialize a promising new vaccine for the prevention of bacterial infections in production and companion animals. The company has obtained the rights to develop animal vaccines against a proprietary antigenic target – dPNAG. That target, developed by Dr. Gerald Pier at Harvard Medical School, holds great promise as a vaccine against wide range of infections. The Company’s lead compound is a conjugated oligosaccharide of PNAG that elicits a protective antibody response against a number of bacterial pathogens associated with human and animal infections.

For the past 2 decades Dr. Pier’s laboratory has focused on the role in virulence and as a vaccine target of the β-1-6 polymer of N-acetyl glucosamine (PNAG) expressed on the surface of various bacteria. This was found to be a critical factor in the virulence and immune response to staphylococcal infections. Bacteria use numerous strategies to avoid host defenses and maintain their capacity to cause serious infections. One well-known strategy is the expression of polysaccharide antigens, such as PNAG, which protect the bacteria from attack by the immune system by blunting or diverting the immune response.

In virulence studies, Dr. Pier’s group showed S. aureus strains that cannot produce PNAG (ica-) had a significantly reduced ability to cause infections in mice.  Such a result is an important component of any immunotherapy development strategy. Bacteria cannot simply avoid the immune therapy by mutating to not produce the target antigen.  In this case, such a mutation would severely cripple the bacterium’s ability to cause infection

While the focus of Dr. Pier’s laboratory has been on the role PNAG in staphylococcal infections it has also been noted that PNAG is also found on a wide range of other bacterial species that cause disease in humans and animals. This suggests that a vaccine could provide protection well beyond the prevention or treatment of S. aureus infections.  Those bacteria are shown the in the table below. 

Development of a Synthetic PNAG Vaccine

The broad antigenic specificity of PNAG extending across multiple bacterial species makes it  an attractive vaccine candidate.  Because chemical derivation of dPNAG from native PNAG is imprecise, a synthetic oligosaccharide with linkers on the reducing termini has been  created.  Synthetic 5-mer GlcNH2 (5GlcNH2) or the 9-mer 9GlcNH2 conjugated to tetanus toxoid (TT) elicited mouse antibodies that mediated opsonic killing of multiple S. aureus strains. As shown below rabbit antibodies to 9GlcNH2-TT bound to PNAG and dPNAG antigens, mediated killing of S. aureus and E. coli, and protected against S. aureus skin abscesses and lethal E. coli peritonitis.  Efficacy of this vaccine has also been demonstrated in animal species (goats, mice and rabbits). Studies are planned to demonstrate its efficacy in production  animals and humns. This chemically derived vaccine could potentially be used to engender protective immunity to the broad range of pathogens that produce surface PNAG.

Immunologic activities of rabbit antisera to 9GlcNH2-TT conjugate vaccine. (A) ELISA-determined titers of antibodies to PNAG, dPNAG, 9GlcNH2, and 9GlcNAc obtained 2 and 6 weeks after the last immunization. (B) Opsonic killing of different S. aureus strains by rabbit antisera to 9GlcNH2-TT obtained 6 weeks after the last immunization. (C) Opsonic killing of two PNAG-positive E. coli strains (J and P) but not a PNAG-negative strain (E. coli H) by rabbit antisera to 9GlcNH2-TT obtained 6 weeks after the last immunization. The level of activity of preimmune sera was subtracted out. C