Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Galan-Navarro, Clara1
  • Rincon-Restrepo, Marcela2
  • Zimmer, Gert3
  • Ollmann Saphire, Erica4
  • Hubbell, Jeffrey A5
  • Hirosue, Sachiko6
  • Swartz, Melody A7
  • Kunz, Stefan8
  • 1 Institute of Microbiology, Lausanne University Hospital. Lausanne, Switzerland; Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering, École Polytechnique Féderal de Lausanne (EPFL), 1015 Lausanne, Switzerland. , (Switzerland)
  • 2 Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering, École Polytechnique Féderal de Lausanne (EPFL), 1015 Lausanne, Switzerland. , (Switzerland)
  • 3 Division of Virology, Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland. , (Switzerland)
  • 4 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, United States. , (United States)
  • 5 Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering, École Polytechnique Féderal de Lausanne (EPFL), 1015 Lausanne, Switzerland; Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL, United States. , (Switzerland)
  • 6 Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering, École Polytechnique Féderal de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: [email protected] , (Switzerland)
  • 7 Laboratory of Lymphatic and Cancer Bioengineering, Institute of Bioengineering, École Polytechnique Féderal de Lausanne (EPFL), 1015 Lausanne, Switzerland; Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL, United States. Electronic address: [email protected] , (Switzerland)
  • 8 Institute of Microbiology, Lausanne University Hospital. Lausanne, Switzerland. Electronic address: [email protected] , (Switzerland)
Type
Published Article
Journal
Virology
Publisher
Elsevier
Publication Date
Dec 01, 2017
Volume
512
Pages
161–171
Identifiers
DOI: 10.1016/j.virol.2017.09.013
PMID: 28963882
Source
Medline
Keywords
License
Unknown

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.

Report this publication

Statistics

Seen <100 times