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Haloarchaeal gas vesicle nanoparticles displaying Salmonella antigens as a novel approach to vaccine development

DasSarma, P and Negi, VD and Balakrishnan, A and Kim, JM and Karan, R and Chakravortty, D and DasSarma, S (2015) Haloarchaeal gas vesicle nanoparticles displaying Salmonella antigens as a novel approach to vaccine development. In: 8th Vaccine and ISV Congress, OCT 26-28, 2014, Philadelphia, PA, pp. 16-23.

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Official URL: http://dx.doi.org/10.1016/j.provac.2015.05.003

Abstract

A safe, effective, and inexpensive vaccine against typhoid and other Salmonella diseases 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 archaeon Halobacterium sp. NRC-1, bioengineered to display highly conserved Salmonella enterica antigens. As the initial antigen for testing, we selected SopB, a secreted inosine phosphate effector protein injected by pathogenic S. enterica bacteria during infection into the host cells. Two highly conserved sopB gene segments near the 3'- region, named sopB4 and sopB5, were each fused to the grIpC gene, 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 with S. enterica serovar Typhimurium 14028 ApmrG-H111-D (DV-STM-07), a live attenuated vaccine strain. Proinflammatory cytokines IFN-y, IL-2, and IL-9 were significantly induced in mice boosted with SopB5-GVNPs, consistent with a robust Thl 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 SopB5GVNPs, indicating that the C-terminal portions of SopB displayed on GVNPs elicit a protective response to Salmonella infection 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 against Salmonella and other diseases.

Item Type: Conference Proceedings
Additional Information: Copy right for this article belongs to the ELSEVIER SCIENCE BV, SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Keywords: Salmonella; Halobacterium; vaccine; nanoparticle; gas vesicle
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Depositing User: Id for Latest eprints
Date Deposited: 15 Oct 2015 07:13
Last Modified: 15 Oct 2015 07:13
URI: http://eprints.iisc.ac.in/id/eprint/52574

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