Oligomeric state of the ZIKV E protein defines protective immune responses
| Autor: | Ashlie Thomas, Michael J. Miley, Aravinda M. de Silva, Cesar A. Lopez, John Forsberg, Alex Brackbill, Helen M. Lazear, Stefan W. Metz, Shaomin Tian |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy Epitope Zika virus Epitopes 0302 clinical medicine Viral Envelope Proteins Chlorocebus aethiops lcsh:Science 0303 health sciences Multidisciplinary Zika Virus Infection Antibodies Monoclonal Recombinant Proteins 3. Good health Flavivirus Female Antibody Protein vaccines medicine.drug_class Science Protein subunit 030106 microbiology 030231 tropical medicine Biology Monoclonal antibody General Biochemistry Genetics and Molecular Biology Virus Article Antibodies 03 medical and health sciences Immune system Antigen medicine Animals Humans Vero Cells 030304 developmental biology Viral Vaccines General Chemistry Zika Virus biology.organism_classification Virology Antibodies Neutralizing Mice Inbred C57BL 030104 developmental biology Viral infection biology.protein lcsh:Q Protein Multimerization |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-7 (2019) |
| DOI: | 10.1101/674424 |
| Popis: | The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines. Many human antibodies that neutralize Zika virus recognize quaternary epitopes on the envelope (E) protein. Here, Metz et al. engineer stable recombinant homodimers of Zika virus E protein and show that it induces neutralizing antibodies in mice that recognize similar epitopes as human antibodies from Zika infected people. |
| Databáze: | OpenAIRE |
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