Phage-Based Vaccine Platforms for Typhoid Fever: A Transformative Approach to Global Health and Antimicrobial Resistance

Abstract

Typhoid fever, caused by Salmonella enterica serovars Typhi and Paratyphi, remains a major public health threat across Africa and Asia and causes substantial annual morbidity. Transmission persists in low- and middle-income countries (LMICs), where access to safe water and sanitation is limited. While improvements in water, sanitation, and hygiene (WASH) are essential, slow implementation makes vaccination the most practical preventive strategy. Current licensed vaccines have limitations, including suboptimal immune coverage in infants, limited duration of protection, and cold-chain requirements. This review examines bacteriophage-based vaccine platforms as emerging preclinical strategies for typhoid prevention. Phage technologies, including phage display, phage DNA, and hybrid models, offer potential advantages such as multivalent antigen display, projected thermostability, and cost-efficient production using bacterial manufacturing systems. Based on animal immunogenicity and proof-of-concept studies, these systems could theoretically induce durable immunity and broaden age-group protection, although their clinical feasibility and scalability remain unproven. We evaluate key technical hurdles, including endotoxin contamination, host-strain engineering, and payload-expression constraints. We also discuss how these potentially low-cost platforms may contribute to global antimicrobial resistance (AMR) mitigation efforts. Although phage-based vaccines remain in the preclinical stage, they represent promising research platforms for advancing vaccine equity and infectious disease resilience, provided regulatory and technical challenges are overcome. However, significant translational gaps must still be bridged before clinical application can be realized.