[논문]Type VI secretion system sheaths as nanoparticles for antigen display

Del Tordello, Elena; Danilchanka, Olga; McCluskey, Andrew J.; Mekalanos, John J.

doi:10.1073/pnas.1524290113

Type VI secretion system sheaths as nanoparticles for antigen display 원문보기

Proceedings of the National Academy of Sciences of the United States of America, v.113 no.11, 2016년, pp.3042 - 3047

Del Tordello, Elena (Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115) , Danilchanka, Olga (Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115) , McCluskey, Andrew J. (Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115) , Mekalanos, John J. (Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115)

Abstract ▼ AI-Helper

SignificanceCritical aspects that limit use of nanoparticles as vaccine delivery systems include the technical difficulty of preparing particles under conditions that allow controlled protein loading and folding. Biologic nanoparticles offer advantages over chemically derived particles that require harsh organic solvents for preparation. Here, we demonstrate that the multimeric sheath structure of the bacterial type 6 secretion system (T6SS) can be exploited to generate particles that display on their surface many copies of specific proteins of interest. T6SS sheaths represent a functional vaccine delivery system with remarkable flexibility due to the ability to biochemically modify these structures to expand or enhance potential immunogenicity.The bacterial type 6 secretion system (T6SS) is a dynamic apparatus that translocates proteins between cells by a mechanism analogous to phage tail contraction. T6SS sheaths are cytoplasmic tubular structures composed of stable VipA-VipB (named for ClpV-interacting protein A and B) heterodimers. Here, the structure of the VipA/B sheath was exploited to generate immunogenic multivalent particles for vaccine delivery. Sheaths composed of VipB and VipA fused to an antigen of interest were purified from Vibrio cholerae or Escherichia coli and used for immunization. Sheaths displaying heterologous antigens generated better immune responses against the antigen and different IgG subclasses compared with soluble antigen alone. Moreover, antigen-specific antibodies raised against sheaths presenting Neisseria meningitidis factor H binding protein (fHbp) antigen were functional in a serum bactericidal assay. Our results demonstrate that multivalent nanoparticles based on the T6SS sheath represent a versatile scaffold for vaccine applications.

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Type VI secretion system sheaths as nanoparticles for antigen display 원문보기

Abstract ▼ AI-Helper

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