Beyond Antibiotics: Rational Design and Clinical Translation of Vaccines and Adjuvants Against Priority Bacterial Pathogens

Bacterial vaccinology is becoming an increasingly important component of the response to antimicrobial resistance (AMR), particularly as the development of new antibiotics remains slow and bacterial pathogens continue to acquire resistance. However, vaccine development for bacteria faces challenges that are less prominent in viral vaccinology, including antigenic and capsular diversity, immune evasion, biofilm formation, intracellular persistence, and pathogen-specific requirements for mucosal or cellular immunity. Recent advances in reverse vaccinology, structural antigen design, glycoconjugate technology, outer membrane vesicles, nucleic acid platforms, and next-generation adjuvants are expanding the range of possible interventions. Nevertheless, major gaps remain in identifying broadly protective antigens, defining reliable correlates of protection, standardizing immune readouts, and predicting clinical efficacy. Improved translational strategies are therefore needed to connect mechanistic discoveries with vaccine candidates that can be evaluated efficiently in humans.This Research Topic aims to advance the rational design, mechanistic understanding, and clinical translation of vaccines and adjuvants targeting priority bacterial pathogens. It will examine how antigen selection, platform engineering, adjuvant activity, and delivery route can be optimized to induce durable, broadly protective immunity. The Topic will also address how correlates of protection can be discovered and validated, how immune evasion and bacterial persistence can be overcome, and how controlled human infection models (CHIMs), early-phase clinical trials, and regulatory science can accelerate development decisions. Contributions should help clarify which preclinical findings are most predictive of human protection and establish practical pathways from antigen discovery to first-in-human evidence.To gather further insights into bacterial vaccine and adjuvant development for priority pathogens, with emphasis on translationally relevant preclinical and clinical research rather than the broader AMR landscape, we welcome articles addressing, but not limited to, the following themes:o Outer membrane vesicle, bioconjugate, glycoconjugate, live-attenuated, vectored, bacterial ghost, and mRNA vaccine platformso Structure-based antigen design, reverse vaccinology, and antigen prioritizationo Rational adjuvant engineering, including STING and TLR agonists, self-adjuvanting scaffolds, and biomimetic nanoadjuvantso Mucosal vaccine delivery and immunity at sites of bacterial infectiono Mechanisms of protection against antigenically diverse bacterial strainso Immune responses that overcome biofilm shielding, intracellular persistence, and pathogen-mediated immune evasiono Discovery, validation, and standardization of correlates of protection and predictive immune readoutso Controlled human infection models and their application to vaccine developmento Early-phase clinical studies, safety, reactogenicity, and dose optimizationo Regulatory-science challenges and translational decision-making for bacterial vaccines and adjuvants Topic editors: Haibo Li, Ji Ma Source: https://www.frontiersin.org/research-topics/85865/beyond-antibiotics-rational-design-and-clinical-translation-of-vaccines-and-adjuvants-against-priority-bacterial-pathogens