Creating Next-Generation Vaccines to Combat Resistant Infections
Ahmed AMR Lab is at the forefront of designing innovative vaccines to prevent infections caused by antimicrobial-resistant pathogens. By leveraging advanced immunological techniques and focusing on the gastrointestinal tract, we aim to create vaccines that provide long-lasting protection against resistant bacteria and fungi.
Despite the well-documented risk factors associated with the development of most infections infections (e.g. those caused by caused by Clostridioides difficile [C. difficile] and vancomycin-resistant Enterococcus [VRE]), there remains a notable absence of effective vaccines to confer protection against multiple pathogens. Previous studies on vaccine candidates have demonstrated varying degrees of success; however, multiple efforts have not translated into effective protection in clinical settings. We hypothesize that enhanced protection can be achieved through the design of multi-antigen vaccines that incorporate proteins from various stages of the bacterial lifecycle. Furthermore, we evaluate the optimal route of administration based on the magnitude and quality of the induced immune response and the level of protection against infection in murine models.
Infections (caused by C. difficile and VRE for example) represent significant challenges in clinical microbiology, particularly in healthcare settings where antibiotic use is prevalent. The risk factors for developing these infections are well established, including antibiotic exposure, advanced age, and underlying health conditions (McFarland, 2008; van der Meer et al., 2010). Despite this knowledge, the lack of effective vaccines remains a critical gap in our ability to prevent these infections.
Previous vaccine studies targeting C. difficile and VRE have shown some promise in preclinical models; however, these candidates have failed to provide adequate protection in clinical trials (Dingle et al., 2010; Kuehne et al., 2010). The limitations of these studies highlight the need for innovative approaches to vaccine design.
We hypothesize that the development of multi-antigen vaccines, which include proteins derived from various stages of the bacterial lifecycle, may yield greater protective efficacy against C. difficile and VRE infections. By targeting multiple antigens, we aim to elicit a broader and more robust immune response, potentially overcoming the limitations observed in previous vaccine trials.
In addition to antigen selection, the route of vaccine administration will be critically evaluated. The ideal route will be determined based on the extent and quality of the induced immune response, as well as the level of protection conferred against subsequent infections in murine models. Routes such as intramuscular, subcutaneous, and mucosal administration will be considered, with the goal of optimizing immunogenicity and protective efficacy.
The development of effective vaccines starting with C. difficile and VRE infections is imperative to reduce the burden of these pathogens in clinical settings. By employing a multi-antigen approach and carefully selecting the route of administration, we aim to enhance the protective efficacy of vaccine candidates. Future studies will focus on the evaluation of these hypotheses through rigorous preclinical testing.
Effective vaccines are essential to reducing reliance on antibiotics and preventing the spread of antimicrobial resistance. By creating novel vaccines, our research contributes to global efforts to prevent resistant infections and improve public health outcomes.
We welcome partnerships with researchers, clinicians, and industry leaders to advance vaccine development efforts. Contact us at ahmed@purdue.edu to explore collaboration opportunities.
