6mty | pdb_00006mty
Crystal structure of a human anti-ZIKV-DENV neutralizing antibody MZ4 isolated following ZPIV vaccination
Structural highlights
Publication Abstract from PubMedZika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. (1-3)). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)(4-7) in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas. Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor.,Dussupt V, Sankhala RS, Gromowski GD, Donofrio G, De La Barrera RA, Larocca RA, Zaky W, Mendez-Rivera L, Choe M, Davidson E, McCracken MK, Brien JD, Abbink P, Bai H, Bryan AL, Bias CH, Berry IM, Botero N, Cook T, Doria-Rose NA, Escuer AGI, Frimpong JA, Geretz A, Hernandez M, Hollidge BS, Jian N, Kabra K, Leggat DJ, Liu J, Pinto AK, Rutvisuttinunt W, Setliff I, Tran U, Townsley S, Doranz BJ, Rolland M, McDermott AB, Georgiev IS, Thomas R, Robb ML, Eckels KH, Barranco E, Koren M, Smith DR, Jarman RG, George SL, Stephenson KE, Barouch DH, Modjarrad K, Michael NL, Joyce MG, Krebs SJ Nat Med. 2020 Feb;26(2):228-235. doi: 10.1038/s41591-019-0746-2. Epub 2020 Feb 3. PMID:32015557[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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