Immune Therapy for Microbial Diseases
Immune therapy for microbial infections, such as vaccines, have been around for over 200 years. Unlike antibiotics, immune therapy works by directing the immune system to target and kill infectious microbes. A critical advantage of immune therapy is that the functional components remain within our body so, unlike antibiotics, resistance does not develop. In addition, because the immune system is not an antibiotic it will target microbes that are sensitive or resistant to antibiotics. As has been learned with Covid, immune therapies are most effective if they are widely utilized.
For bacterial pathogens, surface polysaccharides have been used successfully to vaccinate humans against Streptococcus pneumoniae, Hemophilus influenzae type b, Neisseria meningitidis and Salmonella enterica serovar Typhi. However, efficacy is limited to the specific surface polysaccharide included in vaccines or targeted by monoclonal antibodies. What is needed are broad-spectrum immune therapeutics that target a large number of microbial pathogens such that a single vaccine or antibody therapy can be used to prevent serious infectious diseases.
Immune Therapy for Neuroinflammation
Increasing evidence suggests a pivotal role of immune processes in the pathogenesis of Alzheimer's disease (AD) as well as other chronic disorders, including traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE) and Parkinson's disease. Recent research indicates that PNAG-containing microbial fragments are found in the brains of patients with these diseases, which can induce neuroinflammation and cognitive deficits. Animal models have shown that anti-PNAG therapeutics are able to reduce or remove microbial fragments which is associated with improved cognitive and behavioral function in AD and TBI.
PNAG
A Broad-Spectrum Target
Alopexx’s proprietary immune therapeutics target the conserved microbial surface polysaccharide poly N-acetyl glucosamine (PNAG). PNAG is a critical component of the microbe’s surface allowing it to adhere to tissues and to survive in the body. Beyond the critical role PNAG serves in helping microbes survive, it has a remarkably wide distribution. PNAG is found on the majority of fungal and bacterial microbes. With rare exception, virtually every microbe we have examined has PNAG on its surface. To date over 75 separate microbial pathogens have been found to express PNAG. This wide distribution of PNAG makes it an ideal target for immune therapeutics and provides, for the first time, a broad-spectrum solution.
A Broad-Spectrum Solution
Alopexx’s immune therapeutics targeting PNAG are comprised of a chemically synthesized vaccine and a fully human monoclonal antibody. Importantly, PNAG is a surface polysaccharide produced by microbes in a similar manner as targets of successful vaccines to organisms such as Streptococcus pneumoniae, Neisseria meningitidis and Hemophilus influenzae. Unlike the narrow-spectrum of these vaccines, the PNAG-targeting therapeutics have the potential to prevent infections caused by a broad-spectrum of microbial pathogens.
| Setting | Relevant Areas | Indications |
|---|---|---|
| Infectious Diseases | Prevention in high-risk populations |
|
| Expansion of existing vaccines |
|
|
| Antibiotic resistant organisms |
|
|
| Sexually transmitted diseases |
|
|
| Chronic and difficult to treat infections |
|
|
| Neuroinflammation | Pre-clinical data indicate immunization against PNAG can prevent this tissue destruction in these disease settings. |
|
Our Platform
Natural antibodies to PNAG are common in humans and many animal species but these antibodies do not routinely have robust opsonic killing or immune protection against PNAG-producing microbes. This is due to inadequate engagement of the serum complement co-factor system that is needed for the induction of protective immunity. Thus, broad-based immunity to this antigen rarely develops naturally in human or animal populations.
Alopexx’s major proprietary advance was the recognition that this ineffective natural immunity was due to the high degree of acetylation of the native PNAG molecule. Natural PNAG has many acetyl groups on its surface. Those surface acetyl groups are responsible for inducing an ineffective immune response. The acetyl groups can be removed by chemically altering PNAG. This results in a strong protective immunogen that now targets the backbone of PNAG and avoids participation from the acetyl groups. Targeting the backbone of PNAG leads to the induction of antibody-mediated bacterial killing. Alopexx’s vaccine and antibody target the backbone on native PNAG and provide an effective immune response.
Effective Targeting of PNAG
