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Open AccessArticle

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

Fraunhofer-Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany
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Vaccines 2020, 8(4), 603; https://doi.org/10.3390/vaccines8040603
Received: 26 August 2020 / Revised: 7 October 2020 / Accepted: 9 October 2020 / Published: 13 October 2020
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. View Full-Text
Keywords: Zika virus; E-protein; fusion loop; mutations; vaccine; dengue virus Zika virus; E-protein; fusion loop; mutations; vaccine; dengue virus
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MDPI and ACS Style

Berneck, B.S.; Rockstroh, A.; Fertey, J.; Grunwald, T.; Ulbert, S. A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination. Vaccines 2020, 8, 603. https://doi.org/10.3390/vaccines8040603

AMA Style

Berneck BS, Rockstroh A, Fertey J, Grunwald T, Ulbert S. A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination. Vaccines. 2020; 8(4):603. https://doi.org/10.3390/vaccines8040603

Chicago/Turabian Style

Berneck, Beatrice S.; Rockstroh, Alexandra; Fertey, Jasmin; Grunwald, Thomas; Ulbert, Sebastian. 2020. "A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination" Vaccines 8, no. 4: 603. https://doi.org/10.3390/vaccines8040603

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