A Transition to Targeted or ‘Smart’ Vaccines: How Understanding Commensal Colonization Can Lead to Selective Vaccination

Bacteria represent a group of biological organisms responsible for causing a myriad of human illnesses such as bacteremia, pneumonia, meningitis, and skin infections. Although there have been substantial improvements in treating bacterial diseases, addressing diseases associated with the formation of physiological communities called biofilms remains a challenge. This is due to the complexity of biofilms, both structurally and phenotypically, which complicates the development of comprehensive prophylactic and therapeutic interventions. This situation is exacerbated by the inability of current in vitro and in vivo biofilm models to accurately represent physiological conditions. Unsurprisingly, antigen discovery and validation using such systems often translate poorly into both in vivo and clinical studies. Subsequently, current vaccine solutions often attempt to prevent disease by averting the initial colonization of bacteria, and antibiotics are prescribed to treat infections caused by bacteria that have dispersed from biofilms (e.g., pneumonia and bacteremia); however, these strategies provide an opportunity for niche replacement by non-vaccine-type bacteria and increased antibiotic resistance, respectively. In this article, we provide an overview of the role that biofilms play in bacterial infections and the limitations of current models used to study them. We then highlight recent developments that have improved the accuracy of biofilm models and provide recommendations for using such models for the development of improved vaccine and therapeutic strategies.