title: Haloarchaeal gas vesicle nanoparticles displaying Salmonella SopB antigen reduce bacterial burden when administered with live attenuated bacteria.
abstract: Innovative vaccines against typhoid and other Salmonella diseases that are safe, effective, and inexpensive are urgently needed. In order to address this need, buoyant, self-adjuvating gas vesicle nanoparticles (GVNPs) from the halophilic archaeon Halobacterium sp. NRC-1 were bioengineered to display the highly conserved Salmonella enterica antigen SopB, a secreted inosine phosphate effector protein injected by pathogenic bacteria during infection into the host cell. Two highly conserved sopB gene segments near the 3'-coding region, named sopB4 and B5, were each fused to the gvpC gene, and resulting GVNPs were purified by centrifugally accelerated flotation. Display of SopB4 and B5 antigenic epitopes on GVNPs was established by Western blotting analysis using antisera raised against short synthetic peptides of SopB. Immunostimulatory activities of the SopB4 and B5 nanoparticles were tested by intraperitoneal administration of recombinant GVNPs to BALB/c mice which had been immunized with S. enterica serovar Typhimurium 14028 ΔpmrG-HM-D (DV-STM-07), a live attenuated vaccine strain. Proinflammatory cytokines IFN-γ, IL-2, and IL-9 were significantly induced in mice boosted with SopB5-GVNPs, consistent with a robust Th1 response. After challenge with virulent S. enterica serovar Typhimurium 14028, bacterial burden was found to be diminished in spleen of mice boosted with SopB4-GVNPs and absent or significantly diminished in liver, mesenteric lymph node, and spleen of mice boosted with SopB5-GVNPs, indicating that the C-terminal portions of SopB displayed on GVNPs elicit a protective response to Salmonella infection in mice. SopB antigen-GVNPs were found to be stable at elevated temperatures for extended periods without refrigeration in Halobacterium cells. The results all together show that bioengineered GVNPs are likely to represent a valuable platform for the development of improved vaccines against Salmonella diseases.
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: DasSarma
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Vidya Devi
authors.initials: VD
authors.lastname: Negi
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Arjun
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Karan
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Barnes
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
authors.forename: Folasade
authors.initials: F
authors.lastname: Ekulona
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India. Electronic address: dipa@mcbl.iisc.ernet.in.
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Chakravortty
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA. Electronic address: sdassarma@som.umaryland.edu.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: DasSarma
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D019617:Halobacterium salinarum / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000517:prevention & control; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D022142:Secretory Vesicles / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D004337:Drug Carriers; D022562:Salmonella Vaccines; C489224:SopB protein, Salmonella
keywords: Antigen display; Enteric disease; Haloarchaea; Nanoparticle; Salmonella