Oxidation-sensitive polymersomes as vaccine nanocarriers enhance humoral responses against Lassa virus envelope glycoprotein.

Details

Serval ID
serval:BIB_E934E291FC84
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Oxidation-sensitive polymersomes as vaccine nanocarriers enhance humoral responses against Lassa virus envelope glycoprotein.
Journal
Virology
Author(s)
Galan-Navarro C., Rincon-Restrepo M., Zimmer G., Ollmann Saphire E., Hubbell J.A., Hirosue S., Swartz M.A., Kunz S.
ISSN
1096-0341 (Electronic)
ISSN-L
0042-6822
Publication state
Published
Issued date
12/2017
Peer-reviewed
Oui
Volume
512
Pages
161-171
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Lassa virus (LASV) causes severe hemorrhagic fever with high mortality, yet no vaccine currently exists. Antibodies targeting viral attachment proteins are crucial for protection against many viral infections. However, the envelope glycoprotein (GP)-1 of LASV elicits weak antibody responses due to extensive glycan shielding. Here, we explored a novel vaccine strategy to enhance humoral immunity against LASV GP1. Using structural information, we designed a recombinant GP1 immunogen, and then encapsulated it into oxidation-sensitive polymersomes (PS) as nanocarriers that promote intracellular MHCII loading. Mice immunized with adjuvanted PS (LASV GP1) showed superior humoral responses than free LASV GP1, including antibodies with higher binding affinity to virion GP1, increased levels of polyfunctional anti-viral CD4 T cells, and IgG-secreting B cells. PS (LASV GP1) elicited a more diverse epitope repertoire of anti-viral IgG. Together, these data demonstrate the potential of our nanocarrier vaccine platform for generating virus-specific antibodies against weakly immunogenic viral antigens.

Keywords
A549 Cells, Animals, Female, Gene Expression Regulation, Viral/immunology, Glycoproteins/genetics, Glycoproteins/metabolism, HEK293 Cells, Humans, Immunity, Humoral, Lassa Fever/prevention & control, Lassa virus/physiology, Mice, Mice, Inbred C57BL, Nanostructures/chemistry, Viral Envelope Proteins/genetics, Viral Envelope Proteins/metabolism, Viral Vaccines/immunology, Anti-viral antibodies, Lassa virus, Nanocarrier, Polymersomes, Subunit vaccine
Pubmed
Web of science
Create date
09/10/2017 15:24
Last modification date
20/08/2019 16:11
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