Oxidation-sensitive polymersomes as vaccine nanocarriers enhance humoral responses against Lassa virus envelope glycoprotein
| Autor: | Sachiko Hirosue, Clara Galan-Navarro, Stefan Kunz, Jeffrey A. Hubbell, Gert Zimmer, Melody A. Swartz, Erica Ollmann Saphire, Marcela Rincon-Restrepo |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Gene Expression Regulation Viral Immunogen viruses medicine.disease_cause Epitope law.invention 03 medical and health sciences Mice Lassa Fever Viral Envelope Proteins law Virology medicine Animals Humans Lassa virus Glycoproteins chemistry.chemical_classification biology Viral Vaccines 3. Good health Immunity Humoral Nanostructures Mice Inbred C57BL 030104 developmental biology HEK293 Cells chemistry A549 Cells Humoral immunity biology.protein Recombinant DNA Female Antibody Nanocarriers Glycoprotein |
| Zdroj: | Virology. 512 |
| ISSN: | 1096-0341 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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