Fusion of hIgG1-Fc to 111In-anti-amyloid single domain antibody fragment VHH-pa2H prolongs blood residential time in APP/PS1 mice but does not increase brain uptake

Rotman, Maarten; Welling, Mick M.; Boogaard, Marlinde L. van den; Moursel, Laure Grand; Graaf, Linda M. van der; Buchem, Mark A. van; Maarel, Silvère M. van der; Weerd, Louise van der

doi:10.1016/j.nucmedbio.2015.03.003

Cited by 54 publications

(36 citation statements)

References 44 publications

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“…SdAbs can be readily fused to human Fc-domain to overcome the limitations of the monovalent sdAbs, such as the short blood residential time and lacking antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity 11 . In addition, bivalent sdAbs can be obtained via the disulfide bond formation in Fc hinge area, which was reported to significantly increase sdAb’s activity 12 .…”

Section: Resultsmentioning

confidence: 99%

Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain

Chi

Liu

Wang

et al. 2020

Preprint

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Section: Resultsmentioning

confidence: 99%

Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain

Chi

Liu

Wang

et al. 2020

Preprint

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“…The results of a competitive ligand-binding assay suggested that 3F11 completely blocked the binding between SARS-CoV-2 RBD and ACE2. 29 To overcome the limitations of monovalent sdAbs, 30 sdAbs was fused with human IgG1 Fc fragments. Results showed that the neutralization activity of recombinant 3F11 significantly increased by 10.8-fold in molar concentration with an IC 50 value of 0.0020 µg/ml in a SARS-CoV-2 pseudotyped virus entry assay.…”

Section: Structure and Function Of The Rbd In Sars-cov And Sars-cov-2mentioning

confidence: 99%

Receptor-binding domain-specific human neutralizing monoclonal antibodies against SARS-CoV and SARS-CoV-2

Xiang

Deng

et al. 2020

Sig Transduct Target Ther

115

112

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The outbreaks of severe acute respiratory syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV and SARS-CoV-2, respectively, have posed severe threats to global public health and the economy. Treatment and prevention of these viral diseases call for the research and development of human neutralizing monoclonal antibodies (NMAbs). Scientists have screened neutralizing antibodies using the virus receptor-binding domain (RBD) as an antigen, indicating that RBD contains multiple conformational neutralizing epitopes, which are the main structural domains for inducing neutralizing antibodies and T-cell immune responses. This review summarizes the structure and function of RBD and RBD-specific NMAbs against SARS-CoV and SARS-CoV-2 currently under development.

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“…31 Although several studies have also shown that several VHHs are able to penetrate into the brain in vivo, 28,29,45 BBB crossing by VHH remains highly variable. 30,63 Here, we show that R3VQ-S-(DOTA/Gd) 3 binds the Aß peptide with high specificity and sensitivity and labels amyloid deposits on brain section of a mouse model of amyloidosis. Furthermore, we demonstrated its ability to cross the BBB and to label amyloid deposits after intravenous injection in mice.…”

Section: R3vq-s-(dota/gd) 3 Imaging Probe Crosses the Bbb And Binds Tmentioning

confidence: 77%

Chemically-defined camelid antibody bioconjugate for the magnetic resonance imaging of Alzheimer's disease

Vandesquille

et al. 2017

mAbs

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Today, molecular imaging of neurodegenerative diseases is mainly based on small molecule probes. Alternatively, antibodies are versatile tools that may be developed as new imaging agents. Indeed, they can be readily obtained to specifically target any antigen of interest and their scaffold can be functionalized. One of the critical issues involved in translating antibody-based probes to the clinic is the design and synthesis of perfectly-defined conjugates. Camelid single-domain antibody-fragments (VHHs) are very small and stable antibodies that are able to diffuse in tissues and potentially cross the blood brain barrier (BBB). Here, we selected a VHH (R3VQ) specifically targeting one of the main lesions of Alzheimer's disease (AD), namely the amyloid-beta (Aß) deposits. It was used as a scaffold for the design of imaging probes for magnetic resonance imaging (MRI) and labeled with the contrastophore gadolinium using either a random or site-specific approach. In contrast to the random strategy, the site-specific conjugation to a single reduced cysteine in the C-terminal part of the R3VQ generates a well-defined bioconjugate in a high yield process. This new imaging probe is able to cross the BBB and label Aß deposits after intravenous injection. Also, it displays improved r1 and r2 relaxivities, up to 30 times higher than a widely used clinical contrast agent, and it allows MRI detection of amyloid deposits in post mortem brain tissue of a mouse model of AD. The ability to produce chemically-defined VHH conjugates that cross the BBB opens the way for future development of tailored imaging probes targeting intracerebral antigens.

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Fusion of hIgG1-Fc to 111In-anti-amyloid single domain antibody fragment VHH-pa2H prolongs blood residential time in APP/PS1 mice but does not increase brain uptake

Abstract: Using VHH-Fc conjugates increases the blood half-life of the protein. However, purely extending the time window for brain uptake does not increase BBB passage. Nevertheless, VHH-Fc holds promise for therapeutic applications where a sustained systemic circulation of VHH is advantageous.

Cited by 54 publications

References 44 publications

Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain

Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain

Receptor-binding domain-specific human neutralizing monoclonal antibodies against SARS-CoV and SARS-CoV-2

Chemically-defined camelid antibody bioconjugate for the magnetic resonance imaging of Alzheimer's disease

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