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TitleMimotope discovery as a tool to design a vaccine against Zika and dengue viruses.
Journal, issue, pagesBiotechnol Bioeng, Vol. 120, Issue 9, Page 2658-2671, Year 2023
Publish dateApr 14, 2023
AuthorsEsmeralda Cuevas-Juárez / Arturo Liñan-Torres / Carolina Hernández / Mykhailo Kopylov / Clint S Potter / Bridget Carragher / Octavio T Ramírez / Laura A Palomares /
PubMed AbstractVaccine development against dengue virus is challenging because of the antibody-dependent enhancement of infection (ADE), which causes severe disease. Consecutive infections by Zika (ZIKV) and/or ...Vaccine development against dengue virus is challenging because of the antibody-dependent enhancement of infection (ADE), which causes severe disease. Consecutive infections by Zika (ZIKV) and/or dengue viruses (DENV), or vaccination can predispose to ADE. Current vaccines and vaccine candidates contain the complete envelope viral protein, with epitopes that can raise antibodies causing ADE. We used the envelope dimer epitope (EDE), which induces neutralizing antibodies that do not elicit ADE, to design a vaccine against both flaviviruses. However, EDE is a discontinuous quaternary epitope that cannot be isolated from the E protein without other epitopes. Utilizing phage display, we selected three peptides that mimic the EDE. Free mimotopes were disordered and did not elicit an immune response. After their display on adeno-associated virus (AAV) capsids (VLP), they recovered their structure and were recognized by an EDE-specific antibody. Characterization by cryo-EM and enzyme-linked immunosorbent assay confirmed the correct display of a mimotope on the surface of the AAV VLP and its recognition by the specific antibody. Immunization with the AAV VLP displaying one of the mimotopes induced antibodies that recognized ZIKV and DENV. This work provides the basis for developing a Zika and dengue virus vaccine candidate that will not induce ADE.
External linksBiotechnol Bioeng / PubMed:37058415
MethodsEM (single particle)
Resolution2.36 - 2.42 Å
Structure data

EMDB-28022: Adeno-associated virus type 2 VLP displaying M2 peptide
Method: EM (single particle) / Resolution: 2.42 Å

EMDB-28040: Adeno-associated virus type 2 VLP displaying Linker peptide
Method: EM (single particle) / Resolution: 2.36 Å

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