A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron

Maeda, Ryota; Fujita, Junnosuke; Konishi, Yoshinobu; Kazuma, Yasuhiro; Yamazaki, Hiroyuki; Anzai, Itsuki; Watanabe, Tokiko; Yamaguchi, Keishi; Kasai, Kazuki; Nagata, Kayoko; Yamaoka, Yutaro; Miyakawa, Kei; Ryo, Akihide; Shirakawa, Kotaro; Sato, Kei; Makino, Fumiaki; Matsuura, Yoshiharu; Inoue, Tsuyoshi; Imura, Akihiro; Namba, Keiichi; Takaori‐Kondo, Akifumi

doi:10.1038/s42003-022-03630-3

Cited by 37 publications

(29 citation statements)

References 106 publications

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“…Nanobodies targeting SARS-CoV-2 spike protein were selected as previously described 12 , 13 . Genes of N-terminally PelB (MKYLLPTAAAGLLLLAAQPAMA)-tagged tandem homotrimer of the nanobody connected with two (GGGGS) 4 linkers and C-terminally 6×His-tagged were synthesized and subcloned in the pMES4 vector.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported that two nanobodies, P17 and P86, potently neutralize SARS-CoV-2 VOCs including Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, Delta/B.1.617.2, and Omicron/BA.1/BA.2 12 , 13 . We also determined the epitopes recognized by these nanobodies (P17 and P86) using Cryo-EM.…”

Section: Introductionmentioning

confidence: 99%

“…The epitopes were located on the outer side of RBD; even outer than that recognized by previously reported class 3 human neutralizing Abs. It seems that VHH is small enough to access the hidden clef that is not recognized by human neutralizing Abs 12 , 14 .…”

Section: Introductionmentioning

confidence: 99%

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Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

et al. 2022

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Background SARS-CoV-2 Omicron variants are highly resistant to vaccine-induced immunity and human monoclonal antibodies. Methods We previously reported that two nanobodies, P17 and P86, potently neutralize SARS-CoV-2 VOCs. In this study, we modified these nanobodies into trimers, called TP17 and TP86 and tested their neutralization activities against Omicron BA.1 and subvariant BA.2 using pseudovirus assays. Next, we used TP17 and TP86 nanobody cocktail to treat ACE2 transgenic mice infected with lethal dose of SARS-CoV-2 strains, original, Delta and Omicron BA.1. Results Here, we demonstrate that a novel nanobody TP86 potently neutralizes both BA.1 and BA.2 Omicron variants, and that the TP17 and TP86 nanobody cocktail broadly neutralizes in vitro all VOCs as well as original strain. Furthermore, intratracheal administration of this nanobody cocktail suppresses weight loss and prolongs survival of human ACE2 transgenic mice infected with SARS-CoV-2 strains, original, Delta and Omicron BA.1. Conclusions Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

et al. 2022

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“…Homology models of NIBIC-71 and 7G7/κ Fabs were generated by SWISS-MODEL 32 . The atomic model of S protein 26 and the homology models of the Fabs were manually fitted into the density by using UCSF Chimera 33 and Coot 34 . Figures were prepared by using ChimeraX 35 and PyMOL (Schrödinger, LLC).…”

Section: Methodsmentioning

confidence: 99%

Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein

Otsubo

Minamitani

Kobiyama

et al. 2022

Sci Rep

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal target regions is required to obtain neutralizing antibodies that can counter VOCs. Such regions have not been identified to date. We obtained 2 mAbs, NIBIC-71 and 7G7, using peripheral blood mononuclear cells derived from volunteers who recovered from COVID-19. Both mAbs had neutralizing activity against wild-type SARS-CoV-2 and Delta, but not Omicron. NIBIC-71 binds to the RBD, whereas 7G7 recognizes the N-terminal domain of the S1. In particular, 7G7 inhibited S1/S2 cleavage but not the interaction between the S protein and angiotensin-converting enzyme 2; it suppressed viral entry. Thus, the efficacy of a neutralizing mAb targeting inhibition of S1/2 cleavage was demonstrated. These results suggest that neutralizing mAbs targeting blockade of S1/S2 cleavage are likely to be cross-reactive against various VOCs.

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“…The anti-SARS-CoV-2 monoclonal antibodies demonstrated positive effects in pre-exposure prophylaxis against susceptible variants ( 24 ), prevention of progression to severe COVID-19 ( 25 ), and reduction of patient mortality ( 26 ). In addition, because it can recognize the receptor binding domain (RBD) or other SARS-CoV-2 receptors, nanobodies have also been developed to detect the spike proteins of SARS-CoV-2 variants including Omicron ( 27 ), and show the potential of neutralizing SARS-CoV-2 variants ( 28 – 31 ).…”

Section: Introductionmentioning

confidence: 99%

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis

et al. 2022

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BackgroundSince the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics.MethodsPublications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis.Results1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: “Delta/Omicron variants”, “cytokine storm”, “neutralization/neutralizing antibody”, “T cell”, “BNT162b2”, “mRNA vaccine”, “vaccine effectiveness/safety”, and “long COVID”.ConclusionThis study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.

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A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron

Cited by 37 publications

References 106 publications

Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis

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