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Braz J Microbiol. 2019 Jan;50(1):67-77. doi: 10.1007/s42770-018-0035-0. Epub 2018 Dec 6.

Nano-multilamellar lipid vesicles (NMVs) enhance protective antibody responses against Shiga toxin (Stx2a) produced by enterohemorrhagic Escherichia coli strains (EHEC).

Author information

1
Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1374, Cidade Universitária, São Paulo, SP, 05508-900, Brazil.
2
Unit for Drug Development and Plasmodium Molecular Biology, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
3
Supramolecular Chemistry and Nanotechnology Laboratory, Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
4
Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1374, Cidade Universitária, São Paulo, SP, 05508-900, Brazil. lcsf@usp.br.

Abstract

Microlipid vesicles (MLV) have a broad spectrum of applications for the delivery of molecules, ranging from chemical compounds to proteins, in both in vitro and in vivo conditions. In the present study, we developed a new set of nanosize multilayer lipid vesicles (NMVs) containing a unique combination of lipids. The NMVs enable the adsorption of histidine-tagged proteins at the vesicle surface and were demonstrated to be suitable for the in vivo delivery of antigens. The NMVs contained a combination of neutral (DOPC) and anionic (DPPG) lipids in the inner membrane and an external layer composed of DOPC, cholesterol, and a nickel-containing lipid (DGS-NTA [Ni]). NMVs combined with a recombinant form of the B subunit of the Shiga toxin (rStx2B) produced by certain enterohemorragic Escherichia coli (EHEC) strains enhanced the immunogenicity of the antigen after parenteral administration to mice. Mice immunized with rStx2B-loaded NMVs elicited serum antibodies capable of neutralizing the toxic activities of the native toxin; this result was demonstrated both in vitro and in vivo. Taken together, these results demonstrated that the proposed NMVs represent an alternative for the delivery of antigens, including recombinant proteins, generated in different expression systems.

KEYWORDS:

Delivery system; Lipids vesicles; Multilamellar vesicles; Nanoparticles; Shiga toxin

PMID:
30637647
DOI:
10.1007/s42770-018-0035-0

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