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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
  • Aggregatibacter actinomycetemcomitans
  • Actinobacillus pleuropneumoniae
  • Acinetobacter baumannii
  • E. coli including0157 and other Shiga-toxin producers
  • S. aureus including MRSA
  • S. epidermidis and other coagulase-negative staphylococci
  • Vibrio parahemolyticus
  •  Yersinia pestis
Genes for biosynthetic proteins identified and immunologic confirmation of PNAG expression
  • Bacillus subtilis
  • Bordetella pertussis
  • B. parapertussis
  • B. bronchiseptica
  • Burkholderia cenocepacia complex
  • Enterococcus faecalis
  • Klebsiella pneumoniae
  • Salmonella enterica, multiple serovars including typhi and typhimurium
  • Shigella species
  • Streptococcus agalactiae (Group B streptococcus)
  • Streptococcus pyogenes (Group A streptococcus)
  • Streptococcus pneumoniae (all serogroups)
  • Stenotrophomonas maltopilia
  • Vibrio cholerae
  • Y. entercolitica
  • Y. pseudotuberculosis
Immunologic confirmation of PNAG expression only
  • Aspergillus species
  • Babesia bovis
  • Bacteroides fragilis
  • Borrelia burgdorferi
  • Brucella abortus
  • Burkholderia mallei
  • B. pseudomallei
  • Candida albicans
  • Campylobaccter jejunii
  • Chlamydia trachomatis
  • Clostridium difficle
  • Dirofilaria immitis (heart worm)
  • Enterobacter cloacae
  • Francisella tularensis
  • Fusarium solani
  • Helicobacter pylori
  • Hemophilus ducreyi
  • Hemophilus influenzae
  • Hemophilus parasuis
  • Leptospira serovar Pomona
  • Listeria monocytogenes
  • Mannheimia haemolytica
  • Mycobacterium tuberculosis
  • Neisseria gonorrhoeae
  • Neisseria meningitides
  • Plasmodium species
  • Propionobacterium acnes
  • Rhodococcus equi
  • Salmonella cholerasuis
  • Staphylococcus pseudintermedius
  • Streptococcus dysgalactiae
  • Streptococcus equi
  • Streptococcus suis
  • Streptococcus uberis
  • Theileria equi
  • Trichomonas vaginalis
  • Tritrichomonas foetus

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.

Animal Pathogen Infection Model
Mouse S. aureus Lethal peritonitis
Bacteremia
Skin infection
Corneal keratitis
E. coli Lethal peritonitis
Oral infection with Shiga-toxin producing strains
Burkholderia cenocepacia Lethal peritonitis
A. baumannii Bacteremia
Pneumonia
N. meningitidis serogroup B Neonatal infection
S. pyogenes Lethal infections
L. monocytogenes Lethal infections
S. pneumoniae Pneumonia
Corneal infections
C. albicans Keratitis
P. berghei ANKA Malaria
Horses R. equi Pneumonia in foals  – immunity transferred from vaccinated mares
Pigs A. pleuropneumoniae Pneumonia
Sheep S. aureus Mastitis
Lethal infection
Protection associated with achieving high titer to PNAG

Alopexx Vaccine has filed an Investigational New Drug Application with the FDA. A Phase I clinical study was initiated in the US. The clinical portion of that study has been completed. No adverse events associated with the vaccine were observed. The effect of the vaccine on immunologic responses to PNAG and relevant bacterial pathogens us currently underway. A Phase II trial is currently under development and is planned to begin in 1Q18.

For veterinary use the vaccine has demonstrated significant protection against a serious pathogen in horses –Rhodococcus equi. That bacteria is closely related to tuberculosis which suggests that the vaccine (and antibody) may be effective against that pathogen in humans. Plans are underway to seek USDA approval for the vaccine in 2018.