Platform Overview

Precision Targeting of Pathogens in the Microbiome and Respiratory Tract

Human beings serve as a host to diverse bacterial species that play critical roles in our typical bodily functions. It has been estimated that there are at least as many bacterial cells as human cells within each person that form complex communities. Often, these bacteria serve commensal or even mutualistic roles with their human hosts. However, there are numerous bacterial species that escape from these communities and disseminate into normally sterile areas such as the blood or lungs. This results in serious medical conditions such as septicemia, pneumonia, and meningitis that can become deadly if left untreated. One of the major challenges in healthcare is how to prevent dangerous bacteria from causing disease without disrupting the beneficial communities.

Figure 1. Asymptomatic colonization by bacterial communities that is either commensal or mutualistic.

Figure 2. Release of virulent bacteria from communities. These bacteria can readily invade and damage other areas of the human body.

 

Bacterial communities in the human body often cooperate to form structures known as biofilms. The formation of biofilms problematic for healthcare since they enable the bacteria to resist the immune response and treatments such as antibiotics. To circumvent this challenge, current vaccine strategies endeavor to prevent the initial colonization and biofilm formation by pathogenic bacteria. Unfortunately, this strategy provides a niche for other pathogens to colonize instead. A key example of this phenomenon is the increased prevalence of non-vaccine-type serotypes following the introduction of pneumococcal polysaccharide conjugate vaccines.

Figure 3. Microscope images of bacterial biofilms highlighting common structural features.

Abcombi seeks to shift the paradigms of vaccines and anti-infectives used to combat colonizing pathogens. To do this, we use a clinically predictive biofilm model in conjunction with bioinformatics to identify new classes of antigen candidates that provide a unique protection scheme against colonizing bacteria such as MRSA, Streptococcus pneumoniae, and Group A Streptococcus (strep throat). Once candidates have been identified, we have the capability to rapidly screen numerous antigens to identify unique protective capabilities. This approach has enabled the development of vaccines that target unique / previously undiscovered candidates on commensal bacteria. An added benefit of our approach is the optionality to selectively target only the potentially life-threatening bacterial phenotypes while leaving the harmless, and often beneficial, bacterial microflora unscathed.

Figure 4. Abcombi’s vaccination strategy involves training the immune system to target only virulent bacteria, allowing asymptomatic colonization.

 

In addition, we also employ our disease models for the discovery of therapeutics. Specifically, we are developing an array of broad-acting anti-infective treatments against biofilm-forming bacteria and influenza.