دورية أكاديمية
A conserved set of mutations for stabilizing soluble envelope protein dimers from dengue and Zika viruses to advance the development of subunit vaccines.
| العنوان: | A conserved set of mutations for stabilizing soluble envelope protein dimers from dengue and Zika viruses to advance the development of subunit vaccines. |
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| المؤلفون: | Phan TTN; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Hvasta MG; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Kudlacek ST; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Thiono DJ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Tripathy A; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Nicely NI; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., de Silva AM; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Kuhlman B; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Electronic address: bkuhlman@email.unc.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2022 Jul; Vol. 298 (7), pp. 102079. Date of Electronic Publication: 2022 May 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Dengue Virus*/genetics , Vaccines, Subunit*/genetics , Viral Envelope Proteins*/genetics , Viral Vaccines*/genetics , Zika Virus*/genetics, Antibodies, Neutralizing ; Antibodies, Viral ; Cross Reactions ; Dengue/prevention & control ; Epitopes ; Humans ; Mutation ; Vaccines, Attenuated ; Zika Virus Infection/prevention & control |
| مستخلص: | Dengue viruses (DENV serotypes 1-4) and Zika virus (ZIKV) are related flaviviruses that continue to be a public health concern, infecting hundreds of millions of people annually. The traditional live-attenuated virus vaccine approach has been challenging for the four DENV serotypes because of the need to achieve balanced replication of four independent vaccine components. Subunit vaccines represent an alternative approach that may circumvent problems inherent with live-attenuated DENV vaccines. In mature virus particles, the envelope (E) protein forms a homodimer that covers the surface of the virus and is the major target of neutralizing antibodies. Many neutralizing antibodies bind to quaternary epitopes that span across both E proteins in the homodimer. For soluble E (sE) protein to be a viable subunit vaccine, the antigens should be easy to produce and retain quaternary epitopes recognized by neutralizing antibodies. However, WT sE proteins are primarily monomeric at conditions relevant for vaccination and exhibit low expression yields. Previously, we identified amino acid mutations that stabilize the sE homodimer from DENV2 and dramatically raise expression yields. Here, we tested whether these same mutations raise the stability of sE from other DENV serotypes and ZIKV. We show that the mutations raise thermostability for sE from all the viruses, increase production yields from 4-fold to 250-fold, stabilize the homodimer, and promote binding to dimer-specific neutralizing antibodies. Our findings suggest that these sE variants could be valuable resources in the efforts to develop effective subunit vaccines for DENV serotypes 1 to 4 and ZIKV. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022. Published by Elsevier Inc.) |
| معلومات مُعتمدة: | P30 CA008748 United States CA NCI NIH HHS; P30 CA016086 United States CA NCI NIH HHS; R01 AI161025 United States AI NIAID NIH HHS; R35 GM131923 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: Rosetta; Zika virus; antibody binding; antigen presentation; dengue virus; flavivirus; protein design; protein stability; soluble E dimer; vaccine development |
| المشرفين على المادة: | 0 (Antibodies, Neutralizing) 0 (Antibodies, Viral) 0 (Epitopes) 0 (Vaccines, Attenuated) 0 (Vaccines, Subunit) 0 (Viral Envelope Proteins) 0 (Viral Vaccines) |
| تواريخ الأحداث: | Date Created: 20220601 Date Completed: 20220726 Latest Revision: 20230831 |
| رمز التحديث: | 20230831 |
| مُعرف محوري في PubMed: | PMC9249817 |
| DOI: | 10.1016/j.jbc.2022.102079 |
| PMID: | 35643320 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2022.102079 |