A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms

Zhang, Shuijun; Loy, Thomas; Ng, Thiam-Seng; Lim, Xin Ni; Chew, S.V.; Tan, Tse Yeun; Xu, Meihui; Kostyuchenko, V.A.; Tukijan, Farhana; Shi, Jing; Fink, Katja; Lok, Shee-Mei

doi:10.1016/j.celrep.2020.107584

Cited by 21 publications

(40 citation statements)

References 38 publications

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“…Since the ZIKV outbreak in the Americas in 2015-2016, the potential role of DENV antibodies in ZIKV infection has been examined in a variety of in-vitro, in-vivo, and epidemiological studies. Studies in cell culture [6][7][8][9][10][11][12][13][14][15][16] and immunocompromised mice [6,7,13,[17][18][19] have found a range of outcomes from enhancement of, to protection against, ZIKV infection. As measured by a DENV inhibition ELISA (iELISA) assay, an intermediate baseline DENV-specific antibody titer range of 1:21-1:80 was associated with a greater risk of developing severe dengue disease upon secondary exposure in a human cohort study [2].…”

Section: Introductionmentioning

confidence: 99%

Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques

et al. 2021

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Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

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Section: Introductionmentioning

confidence: 99%

Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques

et al. 2021

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“…For some viruses, especially those that are symmetric, it is feasible to structurally characterize intact viruses using cryo-EM. For example, cryo-EM structures of intact, whole ZIKV have been solved with and without Fabs of Abs bound [ 42 , 43 , 57 , 58 , 59 , 60 , 61 , 62 ]. Viruses with pleomorphic structures (e.g., most enveloped viruses) can also be investigated structurally using cryo-electron tomography [ 63 , 64 , 65 ].…”

Section: Main Bodymentioning

confidence: 99%

“…Given its role in fusion, the E protein is an important target of neutralizing Abs that effectively clear ZIKV, inhibit ZIKV infection in vitro, decrease vertical transmission, and are protective in ZIKV challenge in animal models [ 53 , 54 , 55 , 56 , 72 , 79 , 124 , 125 ] ( Figure 2 C). Structural characterization of Abs that bind the ZIKV E protein have revealed multiple epitopes on the three domains: (1) the conserved FL found on EDII [ 56 , 126 ], (2) EDIII [ 52 , 53 , 54 , 72 , 73 , 127 ], (3) multiple domains of single E protein [ 79 , 80 ], (4) multiple domains spanning an E protein dimer [ 55 , 60 , 79 , 125 , 128 , 129 ], and (5) multiple domains spanning neighboring E dimer pairs [ 61 , 62 , 79 , 129 ]. Abs against the FL in EDII compose a large portion of the response to infection, and because the FL is conserved among flaviviruses, these Abs can cross-react with different flaviviruses [ 56 , 79 , 124 , 125 , 126 , 130 ].…”

Section: Main Bodymentioning

confidence: 99%

How Antibodies Recognize Pathogenic Viruses: Structural Correlates of Antibody Neutralization of HIV-1, SARS-CoV-2, and Zika

Abernathy

Dam

Esswein

et al. 2021

Viruses

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The H1N1 pandemic of 2009-2010, MERS epidemic of 2012, Ebola epidemics of 2013-2016 and 2018-2020, Zika epidemic of 2015-2016, and COVID-19 pandemic of 2019-2021, are recent examples in the long history of epidemics that demonstrate the enormous global impact of viral infection. The rapid development of safe and effective vaccines and therapeutics has proven vital to reducing morbidity and mortality from newly emerging viruses. Structural biology methods can be used to determine how antibodies elicited during infection or vaccination target viral proteins and identify viral epitopes that correlate with potent neutralization. Here we review how structural and molecular biology approaches have contributed to our understanding of antibody recognition of pathogenic viruses, specifically HIV-1, SARS-CoV-2, and Zika. Determining structural correlates of neutralization of viruses has guided the design of vaccines, monoclonal antibodies, and small molecule inhibitors in response to the global threat of viral epidemics.

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“…Residues represented as spheres have been described to be part of B-cell epitopes and contain heavy atoms that fall within the concentric circles: i) D267 (up to 5Å); ii) N153 and R243 (up to 15Å); iii) G102, Q149, E150 and T241 (up to 20Å). ( E–J ) Structural superposition of a monomer of 17D E (ribbon representation) with the modeled kl loop and glycan and one E monomer:Fab complex (flavivirus E from each E:Fab complex isnot shown for clarity; Ab Heavy chain: hot pink; Ab Light chain: Cyan; Fab: Grey): ( E ) DENV-2 EDE1 C10 (PDB: 4UT9) (Rouvinski et al, 2015); ( F ) JEV (Japanese Encephalitis virus) 2F2 (PDB: 5YWO) (Qiu et al, 2018); ( G ) ZIKV (Zika virus) SIGN-3C (PDB: 7BU8) (Zhang et al, 2020); ( H ) WNV (West Nile virus) CR4354 (PDB: 3IYW) (Kaufmann et al, 2010). Antibody domains distal to the E protein were clipped out for clarification in panels F–H.…”

Section: Table S1mentioning

confidence: 99%

Genotype-specific Features Reduce the Susceptibility of South American Yellow Fever Virus Strains to Vaccine-Induced Antibodies

Haslwanter

Lasso

Wec

et al. 2021

Preprint

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SummaryThe resurgence of yellow fever in South America has prompted mitigation through vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a virulent African isolate, and their capacity to induce neutralizing antibodies against the vaccine strain is widely used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. Here, we show that antiviral potency of the polyclonal antibody response in both U.S. and Brazilian vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to genetic changes at two sites in the central domain II of the glycoprotein E, including the acquisition of an N–linked glycosylation site, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for designing updated vaccines.

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A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms

Cited by 21 publications

References 38 publications

Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques

Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques

How Antibodies Recognize Pathogenic Viruses: Structural Correlates of Antibody Neutralization of HIV-1, SARS-CoV-2, and Zika

Genotype-specific Features Reduce the Susceptibility of South American Yellow Fever Virus Strains to Vaccine-Induced Antibodies

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