A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

Gai, Junwei; Ma, Linlin; Li, Guanghui; Zhu, Min; Qiao, Peng; Li, Xiaofei; Zhang, Haiwei; Zhang, Yanmin; Chen, Yadong; Gong, Rui; Wan, Yakun

doi:10.1101/2020.08.09.242867

Cited by 23 publications

(20 citation statements)

References 52 publications

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“…Clinical development of ALX-0171, an inhaled nanobody against RSV, was recently discontinued [ 126 ]. Potent nanobodies have been developed against SARS-CoV-2 [ [127] , [128] , [129] , [130] , [131] , [132] ], with some like mNB6tri [ 130 ] possessing picomolar IC 50 s (2.3 ng/mL) in live SARS-CoV-2 infection assays.…”

Section: Mab Against Sars-cov-2mentioning

confidence: 99%

Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy

Cruz-Teran

Tiruthani

McSweeney³

et al. 2021

Advanced Drug Delivery Reviews

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Section: Mab Against Sars-cov-2mentioning

confidence: 99%

Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy

Cruz-Teran

Tiruthani

McSweeney³

et al. 2021

Advanced Drug Delivery Reviews

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“…Nbs can be efficiently selected against different epitopes on the same antigen and can be easily converted into multivalent formats 9 . The potential of Nbs to address SARS-CoV-2 has been impressively demonstrated by the recent identification of several RBD specific Nbs from naïve/ synthetic libraries [10][11][12] or immunized animals [12][13][14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

NeutrobodyPlex - Nanobodies to monitor a SARS-CoV-2 neutralizing immune response

Wagner

Kaiser

Gramlich

et al. 2020

Preprint

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Facing the worldwide disease progression of COVID-19 caused by the SARS-CoV-2 virus, the situation is highly critical and there is an unmet need for effective vaccination, reliable diagnosis and therapeutic intervention. Neutralizing binding molecules such as antibodies or derivatives thereof have become important tools for acute treatment of COVID-19. Additionally, such binders provide the unique possibility to monitor the emergence and presence of a neutralizing immune response in infected or vaccinated individuals. Here we describe a set of 11 unique nanobodies (Nbs), originated from an immunized alpaca which bind with high affinities to the glycosylated SARS-CoV-2 Spike receptor domain (RBD). Using a multiplex in vitro binding assay we showed that eight of the selected Nbs effectively block the interaction between RBD, S1-domain and homotrimeric Spike protein with the angiotensin converting enzyme 2 (ACE2) as the viral docking site on human cells. According to competitive binding analysis and detailed epitope mapping, we grouped all Nbs blocking the RBD:ACE2 interaction in three distinct Nb-Sets and demonstrated their neutralizing effect with IC50 values in the low nanomolar range in a cell-based SARS-CoV-2 neutralization assay. Tested Nb combinations from different sets showed substantially lower IC50 values in both functional assays indicating a profound synergistic effect of Nbs simultaneously targeting different epitopes within the RBD. Finally, we applied the most potent Nb combinations in a competitive multiplex binding assay which we termed NeutrobodyPlex and detected a neutralizing immune response in plasma samples of infected individuals. We envisage that our Nbs have a high potential for prophylactic as well as therapeutic options and provide a novel approach to screen for a neutralizing immune response in infected or vaccinated individuals thus helping to monitor the immune status or to guide vaccine design.

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“…Camel susceptibility to SARS-CoV-2 is unlikely [ 152 ]. However, preliminary work by Gai and colleagues [ 270 ] applied antibodies collected from camels immunized with SARS-CoV-2 spike receptor-binding domain (RBD) to block the interaction with human ACE-2 receptors.…”

Section: Animal Host Diversity Of Sars-cov-2mentioning

confidence: 99%

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

Hedman¹,

Krawczyk

Helmy

et al. 2021

Pathogens

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Emerging infectious diseases present great risks to public health. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become an urgent public health issue of global concern. It is speculated that the virus first emerged through a zoonotic spillover. Basic research studies have suggested that bats are likely the ancestral reservoir host. Nonetheless, the evolutionary history and host susceptibility of SARS-CoV-2 remains unclear as a multitude of animals has been proposed as potential intermediate or dead-end hosts. SARS-CoV-2 has been isolated from domestic animals, both companion and livestock, as well as in captive wildlife that were in close contact with human COVID-19 cases. Currently, domestic mink is the only known animal that is susceptible to a natural infection, develop severe illness, and can also transmit SARS-CoV-2 to other minks and humans. To improve foundational knowledge of SARS-CoV-2, we are conducting a synthesis review of its host diversity and transmission pathways. To mitigate this COVID-19 pandemic, we strongly advocate for a systems-oriented scientific approach that comprehensively evaluates the transmission of SARS-CoV-2 at the human and animal interface.

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A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

Cited by 23 publications

References 52 publications

Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy

Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy

NeutrobodyPlex - Nanobodies to monitor a SARS-CoV-2 neutralizing immune response

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

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