6MTY

Crystal structure of a human anti-ZIKV-DENV neutralizing antibody MZ4 isolated following ZPIV vaccination

Summary for 6MTY

• Entry DOI: 10.2210/pdb6mty/pdb
• Descriptor: MZ4 Heavy Chain, MZ4 Light Chain (3 entities in total)
• Functional Keywords: zikv-denv, antibody, human, vaccination, antiviral protein, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47063.33

Authors

Sankhala, R.S.,Dussupt, V.,Donofrio, G.,Choe, M.,Modjarrad, K.,Michael, N.L.,Krebs, S.J.,Joyce, M.G. (deposition date: 2018-10-22, release date: 2019-12-25, Last modification date: 2024-10-16)

Primary citation

Dussupt, V.,Sankhala, R.S.,Gromowski, G.D.,Donofrio, G.,De La Barrera, R.A.,Larocca, R.A.,Zaky, W.,Mendez-Rivera, L.,Choe, M.,Davidson, E.,McCracken, M.K.,Brien, J.D.,Abbink, P.,Bai, H.,Bryan, A.L.,Bias, C.H.,Berry, I.M.,Botero, N.,Cook, T.,Doria-Rose, N.A.,Escuer, A.G.I.,Frimpong, J.A.,Geretz, A.,Hernandez, M.,Hollidge, B.S.,Jian, N.,Kabra, K.,Leggat, D.J.,Liu, J.,Pinto, A.K.,Rutvisuttinunt, W.,Setliff, I.,Tran, U.,Townsley, S.,Doranz, B.J.,Rolland, M.,McDermott, A.B.,Georgiev, I.S.,Thomas, R.,Robb, M.L.,Eckels, K.H.,Barranco, E.,Koren, M.,Smith, D.R.,Jarman, R.G.,George, S.L.,Stephenson, K.E.,Barouch, D.H.,Modjarrad, K.,Michael, N.L.,Joyce, M.G.,Krebs, S.J.
Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor.
Nat Med, 26:228-235, 2020

PubMed Abstract: Zika 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. ). 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) 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.

PubMed: 32015557
DOI: 10.1038/s41591-019-0746-2

Experimental method

X-RAY DIFFRACTION (2.951 Å)