title: Haloarchaeal gas vesicle nanoparticles displayingSalmonellaantigens as a novel approach to vaccine development.
abstract: A safe, effective, and inexpensive vaccine against typhoid and otherSalmonelladiseases is urgently needed. In order to address this need, we are developing a novel vaccine platform employing buoyant, self-adjuvanting gas vesicle nanoparticles (GVNPs) from the halophilic archaeonHalobacteriumsp. NRC-1, bioengineered to display highly conservedSalmonella entericaantigens. As the initial antigen for testing, we selected SopB, a secreted inosine phosphate effector protein injected by pathogenicS. entericabacteria during infection into the host cells. Two highly conservedsopBgene segments near the 3'-region, namedsopB4 andsopB5, were each fused to thegvpCgene, and resulting SopB-GVNPs were purified by centrifugally accelerated flotation. Display of SopB4 and SopB5 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 SopB-GVNPs to BALB/c mice which had been immunized withS. entericaserovar 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 virulentS. entericaserovar 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 toSalmonellainfection in mice. SopB antigen-GVNPs were also found to be stable at elevated temperatures for extended periods without refrigeration. The results show that bioengineered GVNPs are likely to represent a valuable platform for antigen delivery and development of improved vaccines againstSalmonellaand other diseases.
authors.affiliation: University of Maryland School of Medicine, USA.
authors.forename: P
authors.initials: P
authors.lastname: DasSarma
authors.affiliation: National Institute of Technology, India; Indian Institute of Science, India.
authors.forename: V D
authors.initials: VD
authors.lastname: Negi
authors.affiliation: Indian Institute of Science, India.
authors.forename: A
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: University of Maryland School of Medicine, USA; PuKyong National University, Republic of Korea.
authors.forename: J-M
authors.initials: JM
authors.lastname: Kim
authors.affiliation: University of Maryland School of Medicine, USA.
authors.forename: R
authors.initials: R
authors.lastname: Karan
authors.affiliation: Indian Institute of Science, India.
authors.forename: D
authors.initials: D
authors.lastname: Chakravortty
authors.affiliation: University of Maryland School of Medicine, USA.
authors.forename: S
authors.initials: S
authors.lastname: DasSarma
keywords: Halobacterium; Salmonella; gas vesicle; nanoparticle; vaccine