Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants

Ishimaru, Hanako; Nishimura, Mitsuhiro; Tjan, Lidya Handayani; Sutandhio, Silvia; Marini, Maria Istiqomah; Effendi, Gema Barlian; Shigematsu, Hideki; Kato, Kuniki; Hasegawa, Natsumi; Aoki, Kaito; Kurahashi, Yukiya; Furukawa, Koichi; Shinohara, M; Nakamura, Tomoka; Arii, Jun; Nagano, Tatsuya; Nakamura, Sachiko; Sano, Shigeru; Iwata, Sachiyo; Okamura, Shingo; Mori, Yasuko

doi:10.1128/jvi.00286-23

Cited by 5 publications

(17 citation statements)

References 42 publications

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“…We observed that MO11 did not bind to the spike RBD of all of the variants tested ( Fig. 3B ), in contrast to the RBD-binding antibody MO7 isolated in our earlier work ( 7 ), indicating that the recognition site of MO11 is outside of the RBD.…”

Section: Resultssupporting

confidence: 82%

“…A human monoclonal antibody, MO11, was isolated from B cells of a convalescent COVID-19 patient who had been infected by SARS-CoV-2 D614G assumed from the onset period (July 2020) and then received three doses of an mRNA vaccination (Table S1) via the procedure described in our earlier study ( 7 ). The neutralizing activity of MO11 against SARS-CoV-2 variants was quantitatively evaluated by a plaque reduction assay using the authentic virus of major SARS-CoV-2 variants: a variant harboring spike D614G mutation (hereafter, D614G), Delta, Omicron BA.1, BA.2, BA.2.75, BA.5, BQ.1.1, XBB.1, XBB.1.5, XBB.1.16, and EG.5.1.…”

Section: Resultsmentioning

confidence: 50%

“…The IC 50 range was 103–883 ng/mL ( Fig. 2A and C ), showing a potency compared to the RBD-targeting antibody MO1 with IC 50 15.67 ng/mL for BA.5 reported in our previous study ( 7 ). Of note, complete inhibition was observed at the 1–10 µg/mL range of MO11 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous attempt to isolate cross-neutralizing antibodies from human blood cells led to the identification of a prospective neutralizing antibody, MO1, that can neutralize the BA.5 variant by targeting a conserved epitope in the RBD ( 7 ). However, two newly emerged variants, XBB.1 and BQ.1.1, escaped from MO1 as well as other antibodies by harboring mutations in the RBD.…”

Section: Introductionmentioning

confidence: 99%

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Epitopes of an antibody that neutralizes a wide range of SARS-CoV-2 variants in a conserved subdomain 1 of the spike protein

Ishimaru,

Nishimura,

Shigematsu

et al. 2024

J Virol

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The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, enabling the virus to escape from host immunity by changing its spike antigen, while biased toward the receptor-binding domain and N-terminal domain. Here, we isolated a novel pan-SARS-CoV-2 neutralizing antibody (which we named MO11) for even the recent dominators XBB.1.16 and EG.5.1, from a convalescent patient who had received three doses of an original mRNA COVID-19 vaccination. A cryo-electron microscopy analysis of the spike-MO11 complex at 2.3 Å atomic resolution revealed that it recognizes a conserved epitope hidden behind a glycan shield at N331 on subdomain 1 (SD1), holding both the N- and C-terminal segments comprising SD1. Our identification of MO11 unveiled the functional importance of SD1 for the spike’s function, and we discuss the potential availability of a novel common epitope among the SARS-CoV-2 variants. IMPORTANCE Novel severe acute respiratory syndrome coronavirus 2 variants with immune evasion ability are still repeatedly emerging, nonetheless, a part of immunity developed in responding to the antigen of earlier variants retains efficacy against recent variants irrespective of the numerous mutations. In exploration for the broadly effective antibodies, we identified a cross-neutralizing antibody, named MO11, from the B cells of the convalescent patient. MO11 targets a novel epitope in subdomain 1 (SD1) and was effective against all emerging variants including XBB.1.16 and EG.5.1. The neutralizing activity covering from D614G to EG.5.1 variants was explained by the conservation of the epitope, and it revealed the importance of the subdomain on regulating the function of the antigen for viral infection. Demonstrated identification of the neutralizing antibody that recognizes a conserved epitope implies basal contribution of such group of antibodies for prophylaxis against COVID-19.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 50%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Epitopes of an antibody that neutralizes a wide range of SARS-CoV-2 variants in a conserved subdomain 1 of the spike protein

Ishimaru,

Nishimura,

Shigematsu

et al. 2024

J Virol

Self Cite

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“…However, cell-free systems are not suitable for the expression of more complicated protein formats such as scFvs (single chain fragment variables) and Fabs (fragment antigen binding). While there has been studies reporting the successful expression of scFvs and Fabs in cell-free systems 27,28,29,30,31 , our first hand experience indicates that cell-free systems are not reliable for the expression of these protein formats.…”

Section: Case Studiesmentioning

confidence: 88%

parSEQ:Probe and Rescue Sequencing for Advanced Variant Retrieval from DNA Pool

Houmani,

Peterkin,

Antoun

et al. 2023

Preprint

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Modern protein engineering is powered by sequence-function data-sets. We have developed parSEQ, a platform that maximizes the capture of these protein sequence-function data-sets through a sequence-first-screen-later approach. parSEQ relies on Next-Generation Sequencing (NGS) to reverse the conventional screen-first-sequence-later workflow. This allows for the high-throughput retrieval of variant sequences from DNA pools, ensuring that every screened variant’s functional data is paired with its sequence data. This report details parSEQ’s methodology and its integration into various protein engineering workflows. Through several case studies, we illustrate parSEQ’s broad applicability. These case studies describe the use of parSEQ for high-throughput variant DNA-template retrieval, expression-ready bacterial clone isolation, sourcing DNA for denovo designed proteins, and preparing targeted mutational libraries. Our findings suggest that parSEQ’s approach to capturing sequence-function data-sets can advance protein engineering efforts, particularly in the age of artificial intelligence and machine learning.

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Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

Inoue,

Yamamoto,

Sato

et al. 2024

iScience

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Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants

Cited by 5 publications

References 42 publications

Epitopes of an antibody that neutralizes a wide range of SARS-CoV-2 variants in a conserved subdomain 1 of the spike protein

Epitopes of an antibody that neutralizes a wide range of SARS-CoV-2 variants in a conserved subdomain 1 of the spike protein

parSEQ:Probe and Rescue Sequencing for Advanced Variant Retrieval from DNA Pool

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

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