Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus

Wang, Qihui; Ma, Tian; Wu, Yan; Chen, Zhihai; Zeng, Hui; Tong, Zhou; Gao, Feng; Qi, Jianxun; Zhao, Zhennan; Chai, Yan; Yang, Huabing; Wong, Gary; Bi, Yang; Wu, Lili; Shi, Rui; Yang, Mi Young; Song, Jian; Jiang, Haihai; An, Zhiqiang; Wang, Junzhi; Yilma, Tilahun; Shi, Yi; Liu, William J.; Liang, Mifang; Qin, Chuan; Gao, George F.; Yan, Jinghua

doi:10.1038/s41564-019-0411-z

Cited by 45 publications

(70 citation statements)

References 42 publications

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“…We expressed COVID-19 virus RBD protein as bait to isolate specific single memory B-cells from COVID-19 patient peripheral blood mononuclear cells (PBMCs). The variable regions encoding the heavy and light chain were each amplified from separate single B cells, and then were cloned into a pCAGGS vector with the constant region to produce IgG1 antibodies as described previously (17). Seventeen paired B cell clones were amplified, three of which were identical (B5, B59 and H1).…”

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confidence: 99%

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Wang

Shen

et al. 2020

Science

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Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. B38 and H4 block the binding between virus S-protein RBD and cellular receptor ACE2. A competition assay indicates their different epitopes on the RBD, making them a potential virus-targeting MAb-pair to avoid immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibodybased therapeutics and provide a structural basis for rational vaccine design.

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confidence: 99%

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Wang

Shen

et al. 2020

Science

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“…30 In Rift Valley fever, pre-exposure passive antibody transfer is well-established to provide protection, 22,[31][32][33] and one study performed in mice demonstrated that administration of a neutralizing antibody 1 day post infection, but before clinical disease was manifest, improved survival. 34 However, there are no published studies that address whether antibody transfer is protective once clinical disease is established, and the utility of antibodies as therapy for RVFV infection has not yet been explored.…”

Section: Discussionmentioning

confidence: 99%

Rift Valley fever virus vaccination induces long-lived, antigen-specific human T cell responses

et al. 2020

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Rift Valley fever virus (RVFV) is a zoonotic arbovirus of clinical significance in both livestock and humans. A formalin-inactivated virus preparation was initially developed for human use and tested in laboratory workers in the 1960s. Vaccination resulted in generation of neutralizing antibody titers in most recipients, but neutralization titers waned over time, necessitating frequent booster doses. In this study, T cell-based immune responses to the formalin-inactivated vaccine were examined in a cohort of seven individuals who received between 1 and 6 doses of the vaccine. RVFV-specific T cell responses were detectable up to 24 years post vaccination. Peripheral blood mononuclear cells from this cohort of individuals were used to map out the viral epitopes targeted by T cells in humans. These data provide tools for assessing human RVFV-specific T cell responses and are thus a valuable resource for future human RVFV vaccine efforts.npj Vaccines (2020) 5:17 ; https://doi.

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“…In 2018, Allen et al isolated some NAbs from rabbits, which were directed to the membrane-distal domain of RVFV Gn and can preclude virus entry into a host cell [21]. In 2019, Wang et al isolated eight Gn-specific NAbs from a convalescent RVF patient that can block the binding of virions to the host cells [22].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Two Neutralizing Antibodies against Rift Valley Fever Virus Gn Protein

Meng

Zhang²,

Zhang

et al. 2020

Viruses

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The Rift Valley fever virus (RVFV) is an arthropod-borne virus that can not only cause severe disease in domestic animals but also in humans. However, the licensed vaccines or available therapeutics for humans do not exist. Here, we report two Gn-specific neutralizing antibodies (NAbs), isolated from a rhesus monkey immunized with recombinant human adenoviruses type 4 expressing Rift Valley fever virus Gn and Gc protein (rHAdV4-GnGcopt). The two NAbs were both able to protect host cells from RVFV infection. The interactions between NAbs and Gn were then characterized to demonstrate that these two NAbs might preclude RVFV glycoprotein rearrangement, hindering the exposure of fusion loops in Gc to endosomal membranes after the virus invades the host cell. The target region for the two NAbs is located in the Gn domain III, implying that Gn is a desired target for developing vaccines and neutralizing antibodies against RVFV.

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Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus

Cited by 45 publications

References 42 publications

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Rift Valley fever virus vaccination induces long-lived, antigen-specific human T cell responses

Characterization of Two Neutralizing Antibodies against Rift Valley Fever Virus Gn Protein

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