Combination of lytic phage Sal-P001 and RAST002 vaccine induces complete protection against homologous and heterologous Salmonella strains.

Nontyphoidal Salmonella infections remain a major global health concern and were exacerbated by increasing antimicrobial resistance. In this study, a lytic bacteriophage, SalP001, was isolated from wastewater collected at a poultry farm. Transmission electron microscopy identified Sal-P001 as a myovirus. The phage exhibited an optimal multiplicity of infection of 0.1, a latent period of 20 min, a burst period of 20-100 min, and a burst size of 458 PFU/cell. Sal-P001 remained stable over a broad temperature (37-72 °C) and pH (2-12) range. We further evaluated the combined use of Sal-P001 with RAST002, a previously developed live attenuated Salmonella vaccine. Combined administration induced robust systemic and mucosal immune responses. Notably, mice receiving the combined treatment achieved 100% survival following challenge with multiple Salmonella serotypes. These findings highlight the potential of integrating bacteriophage application with vaccination as an effective strategy to enhance protection against Salmonella infections.