Layering vaccination with antibiotic therapy results in protection and clearance of Burkholderia pseudomallei in Balb/c mice

Infect Immun. 2024 Mar 12;92(3):e0045523. doi: 10.1128/iai.00455-23. Epub 2024 Jan 30.

Abstract

Melioidosis is a disease that is difficult to treat due to the causative organism, Burkholderia pseudomallei being inherently antibiotic resistant and it having the ability to invade, survive, and replicate in an intracellular environment. Combination therapy approaches are routinely being evaluated in animal models with the aim of improving the level of protection and clearance of colonizing bacteria detected. In this study, a subunit vaccine layered with the antibiotic finafloxacin was evaluated in vivo against an inhalational infection with B. pseudomallei in Balb/c mice. Groups of mice vaccinated, infected, and euthanized at antibiotic initiation had a reduced bacterial load compared to those that had not been immunized. In addition, the subunit vaccine provided a synergistic effect when it was delivered with a CpG ODN and finafloxacin was initiated at 48 h post-challenge. Vaccination was also shown to improve the outcome, in a composite measure of survival and clearance. In summary, layering a subunit vaccine with the antibiotic finafloxacin is a promising therapeutic alternative for use in the treatment of B. pseudomallei infections.

Keywords: Balb/c; Burkholderia pseudomallei; finafloxacin; layered defence; melioidosis; subunit vaccine.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Burkholderia pseudomallei*
  • Disease Models, Animal
  • Melioidosis* / drug therapy
  • Melioidosis* / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Vaccination
  • Vaccines, Subunit

Substances

  • Anti-Bacterial Agents
  • Vaccines, Subunit