Alopexx Vaccine, LLC is developing a vaccine against a proprietary antigenic target – dPNAG. That target, developed by Dr. Gerald B. Pier and colleagues at Harvard Medical School, holds great promise as a vaccine against a wide range of pathogens and infections. The Company’s lead compound, AV0328, is a conjugated oligosaccharide of dPNAG that elicits a protective antibody response against a number of microbial pathogens associated with human and animal infections.
For the past 2 decades Dr. Pier’s laboratory has focused on the role of the β-1-6 polymer of N-acetyl glucosamine (PNAG) in virulence and as a vaccine target.. PNAG is expressed on the surface of various bacteria, fungi and protozoan organisms, functioning essentially as a conserved capsule. PNAG has been shown to be a critical factor in the virulence of many organism and has a profound ability to avoid eliciting an effective immune response. Bacterial strains that lose the ability to produce PNAG generally have a significantly reduced ability to cause infections.
While the focus of Dr. Pier’s laboratory has been on the role of PNAG in staphylococcal infections, it has been noted that PNAG is also found on a wide range of other bacterial, fungal and parasitic pathogens that cause disease in humans and animals (PNAS 110:E2209-2218, 2013). This suggests that a vaccine could provide protection well beyond the prevention or treatment of S. aureus infections. Many of those pathogens are shown in the table below.
|PNAG Expression Determination||Bacterial Species|
|Genes for biosynthetic proteins identified, polysaccharide isolated, immunologic confirmation of PNAG expression||
|Genes for biosynthetic proteins identified and immunologic confirmation of PNAG expression||
|Immunologic confirmation of PNAG expression only||
AV0328 Human & Veterinary Development
The following is a current list of studies that have demonstrated the efficacy of immunotherapy directed against PNAG in treating or preventing a wide range of infections. Of note, the studies in pigs, sheep and horses have utilized pathogens relevant to those species as opposed a more artificial situation where human pathogens are utilized in laboratory settings.
|Mouse||S. aureus||Lethal peritonitis
|E. coli||Lethal peritonitis
Oral infection with Shiga-toxin producing strains
|Burkholderia cenocepacia||Lethal peritonitis|
|N. meningitidis serogroup B||Neonatal infection|
|S. pyogenes||Lethal infections|
|L. monocytogenes||Lethal infections|
|P. berghei ANKA||Malaria|
|Horses||R. equi||Pneumonia in foals – immunity transferred from vaccinated mares|
Protection associated with achieving high titer to PNAG
Alopexx plans to file an Investigational New Drug Application with the FDA in early 2016 and initiate a Phase I clinical study in the U.S.