Cargando…

A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination

Zika virus (ZIKV) is a zoonotic, human pathogenic, and mosquito-borne flavivirus. Its distribution is rapidly growing worldwide. Several attempts to develop vaccines for ZIKV are currently ongoing. Central to most vaccination approaches against flavivirus infections is the envelope (E) protein, whic...

Descripción completa

Detalles Bibliográficos
Autores principales: Berneck, Beatrice Sarah, Rockstroh, Alexandra, Fertey, Jasmin, Grunwald, Thomas, Ulbert, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712286/
https://www.ncbi.nlm.nih.gov/pubmed/33066262
http://dx.doi.org/10.3390/vaccines8040603
_version_ 1783618339866673152
author Berneck, Beatrice Sarah
Rockstroh, Alexandra
Fertey, Jasmin
Grunwald, Thomas
Ulbert, Sebastian
author_facet Berneck, Beatrice Sarah
Rockstroh, Alexandra
Fertey, Jasmin
Grunwald, Thomas
Ulbert, Sebastian
author_sort Berneck, Beatrice Sarah
collection PubMed
description Zika virus (ZIKV) is a zoonotic, human pathogenic, and mosquito-borne flavivirus. Its distribution is rapidly growing worldwide. Several attempts to develop vaccines for ZIKV are currently ongoing. Central to most vaccination approaches against flavivirus infections is the envelope (E) protein, which is the major target of neutralizing antibodies. Insect-cell derived, recombinantly expressed variants of E from the flaviviruses West Nile and Dengue virus have entered clinical trials in humans. Also for ZIKV, these antigens are promising vaccine candidates. Due to the structural similarity of flaviviruses, cross-reactive antibodies are induced by flavivirus antigens and have been linked to the phenomenon of antibody-dependent enhancement of infection (ADE). Especially the highly conserved fusion loop domain (FL) in the E protein is a target of such cross-reactive antibodies. In areas where different flaviviruses co-circulate and heterologous infections cannot be ruled out, this is of concern. To exclude the possibility that recombinant E proteins of ZIKV might induce ADE in infections with related flaviviruses, we performed an immunization study with an insect-cell derived E protein containing four mutations in and near the FL. Our data show that this mutant antigen elicits antibodies with equal neutralizing capacity as the wildtype equivalent. However, it induces much less serological cross-reactivity and does not cause ADE in vitro. These results indicate that mutated variants of the E protein might lead to ZIKV and other flavivirus vaccines with increased safety profiles.
format Online
Article
Text
id pubmed-7712286
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77122862020-12-04 A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination Berneck, Beatrice Sarah Rockstroh, Alexandra Fertey, Jasmin Grunwald, Thomas Ulbert, Sebastian Vaccines (Basel) Article Zika virus (ZIKV) is a zoonotic, human pathogenic, and mosquito-borne flavivirus. Its distribution is rapidly growing worldwide. Several attempts to develop vaccines for ZIKV are currently ongoing. Central to most vaccination approaches against flavivirus infections is the envelope (E) protein, which is the major target of neutralizing antibodies. Insect-cell derived, recombinantly expressed variants of E from the flaviviruses West Nile and Dengue virus have entered clinical trials in humans. Also for ZIKV, these antigens are promising vaccine candidates. Due to the structural similarity of flaviviruses, cross-reactive antibodies are induced by flavivirus antigens and have been linked to the phenomenon of antibody-dependent enhancement of infection (ADE). Especially the highly conserved fusion loop domain (FL) in the E protein is a target of such cross-reactive antibodies. In areas where different flaviviruses co-circulate and heterologous infections cannot be ruled out, this is of concern. To exclude the possibility that recombinant E proteins of ZIKV might induce ADE in infections with related flaviviruses, we performed an immunization study with an insect-cell derived E protein containing four mutations in and near the FL. Our data show that this mutant antigen elicits antibodies with equal neutralizing capacity as the wildtype equivalent. However, it induces much less serological cross-reactivity and does not cause ADE in vitro. These results indicate that mutated variants of the E protein might lead to ZIKV and other flavivirus vaccines with increased safety profiles. MDPI 2020-10-13 /pmc/articles/PMC7712286/ /pubmed/33066262 http://dx.doi.org/10.3390/vaccines8040603 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Berneck, Beatrice Sarah
Rockstroh, Alexandra
Fertey, Jasmin
Grunwald, Thomas
Ulbert, Sebastian
A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination
title A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination
title_full A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination
title_fullStr A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination
title_full_unstemmed A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination
title_short A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination
title_sort recombinant zika virus envelope protein with mutations in the conserved fusion loop leads to reduced antibody cross-reactivity upon vaccination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712286/
https://www.ncbi.nlm.nih.gov/pubmed/33066262
http://dx.doi.org/10.3390/vaccines8040603
work_keys_str_mv AT berneckbeatricesarah arecombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT rockstrohalexandra arecombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT ferteyjasmin arecombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT grunwaldthomas arecombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT ulbertsebastian arecombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT berneckbeatricesarah recombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT rockstrohalexandra recombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT ferteyjasmin recombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT grunwaldthomas recombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination
AT ulbertsebastian recombinantzikavirusenvelopeproteinwithmutationsintheconservedfusionloopleadstoreducedantibodycrossreactivityuponvaccination