Single-Domain Antibodies Efficiently Neutralize SARS-CoV-2 Variants of Concern

Favorskaya, I. A.; Shcheblyakov, Dmitry V.; Esmagambetov, Ilias B.; Dolzhikova, Inna V.; Alekseeva, Irina A; Korobkova, Anastasia I; Voronina, Daria V.; Ryabova, Ekaterina I.; Derkaev, Artem A.; Kovyrshina, Anna V.; Iliukhina, Anna A.; Ботиков, А. Г.; Voronina, Olga; Egorova, Daria A; Zubkova, Olga V.; Рыжова, Н. Н.; Aksenova, Ekaterina I.; Kunda, Marina S.; Logunov, Denis Y.; Naroditsky, Boris S.; Гинцбург, А Л

doi:10.3389/fimmu.2022.822159

Cited by 28 publications

(20 citation statements)

References 48 publications

(56 reference statements)

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“…The technique of Fc-fused single-domain antibody development was described previously (Godakova et al, 2019 ; Esmagambetov et al, 2021 ; Voronina et al, 2021 ; Favorskaya et al, 2022 ). The nucleotide sequence encoding B11-Fc antibody was synthesized at Evrogen Company (Moscow, Russia) and cloned into the pAAV–EGFP Control Vector plasmid instead of the EGFP gene at the EcoRI and XbaI restriction sites, thus obtaining the pAAV-B11-Fc plasmid.…”

Section: Methodsmentioning

confidence: 99%

“…VHH fusion with the canonical immunoglobulin Fc fragment allows VHH-Fc to significantly increase their neutralizing activity and serum half-life (Godakova et al, 2019 ). It has been shown in particular that HC-only antibodies or VHHs derived from HC-only antibodies produced by camelids demonstrate protection not only against various non-toxin diseases (Shcheblyakov et al, 2019 ; Favorskaya et al, 2022 ) but also strong anti-BoNT activities in animal models (Yu et al, 2009 ; Swain et al, 2010 ; Tremblay et al, 2010 ) comparable to those of canonical antibodies (Garcia-Rodriguez et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

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rAAV expressing recombinant neutralizing antibody for the botulinum neurotoxin type A prophylaxis

et al. 2022

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Botulinum neurotoxin (BoNT) is one of the most dangerous bacterial toxins and a potential biological weapon component. BoNT mechanism of pathological action is based on inhibiting the release of neurotransmitters from nerve endings. To date, anti-BoNT therapy is reduced to the use of horse hyperimmune serum, which causes many side effects, as well as FDA-approved drug BabyBig which consists of human-derived anti-BoNT antibodies (IgG) for infant botulinum treatment. Therapeutics for botulism treatment based on safer monoclonal antibodies are undergoing clinical trials. In addition, agents have been developed for the specific prevention of botulism, but their effectiveness has not been proved. In this work, we have obtained a recombinant adeno-associated virus (rAAV-B11-Fc) expressing a single-domain antibody fused to the human IgG Fc-fragment (B11-Fc) and specific to botulinum toxin type A (BoNT/A). We have demonstrated that B11-Fc antibody, expressed via rAAV-B11-Fc treatment, can protect animals from lethal doses of botulinum toxin type A, starting from day 3 and at least 120 days after administration. Thus, our results showed that rAAV-B11-Fc can provide long-term expression of B11-Fc-neutralizing antibody in vivo and provide long-term protection against BoNT/A intoxication. Consequently, our study demonstrates the applicability of rAAV expressing protective antibodies for the prevention of intoxication caused by botulinum toxins.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

rAAV expressing recombinant neutralizing antibody for the botulinum neurotoxin type A prophylaxis

et al. 2022

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“…Гуманизированное моноклональное антитело GamXRH19 и тяжелоцепочечное моноклональное антитело GamP2C5 являются компонентами препарата ГамКовиМаб (лекарственный препарат для экстренной профилактики и ранней этиотропной терапии коронавирусной инфекции, вызываемой вирусом SARS-СoV-2, на основе гуманизированных моноклональных антител, раствор для инфузий, находящийся на II фазе клинических исследований 4 ), производства филиала «Медгамал» ФГБУ «НИЦЭМ им. Н.Ф.…”

Section: материалыunclassified

“…Кроме того, данный подход можно применять для изучения специфической активности препаратов для терапии и экстренной профилактики COVID-19. В частности, уровень специфического сигнала к рекомбинантному RBD в непрямом ИФА являлся одним из критериев отбора однодоменных антител [4] при разработке препарата ГамКовиМаб, успешно прошедшего первую фазу клинических исследований.…”

Section: результаты и обсуждениеunclassified

Production and characterisation of a SARS-CoV-2 S-protein RBD homodimer with increased avidity for specific antibodies

Derkaev

Ryabova

Prokofiev

et al. 2023

Biological Products. Prevention, Diagnosis, Treatment

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Monitoring of the proportion of immune individuals and the effectiveness of vaccination in a population involves evaluation of several important parameters, including the level of virus-neutralising antibodies. In order to combat the COVID-19 pandemic, it is essential to develop approaches to detecting SARS-CoV-2 neutralising antibodies by safe, simple and rapid methods that do not require live viruses. To develop a test system for enzyme-linked immunosorbent assay (ELISA) that detects potential neutralising antibodies, it is necessary to obtain a highly purified recombinant receptor-binding domain (RBD) of the spike (S) protein with high avidity for specific antibodies. The aim of the study w as t o obtain and characterise a SARSCoV-2 S-protein RBD homodimer and a recombinant RBD-expressing cell line, as well as to create an ELISA system for detecting potential neutralising antibodies. Materials and methods: the genetic construct was designed in silico. To generate a stable producer cell line, the authors transfected CHO-S cells, subjected them to antibiotic pressure, and selected the optimal clone. To isolate monomeric and homodimeric RBD forms, the authors purified the recombinant RBD by chromatographic methods. Further, they analysed the activity of the RBD forms by Western blotting, bio-layer interferometry, and indirect ELISA. The analysis involved monoclonal antibodies GamXRH19, GamP2C5, and h6g3, as well as serum samples from volunteers vaccinated with Gam-COVID-Vac (Sputnik V) and unvaccinated ones. Results: the authors produced the CHO-S cell line for stable expression of the recombinant SARS-CoV-2 S-protein RBD. The study demonstrated the recombinant RBD’s ability to homodimerise after fed-batch cultivation of the cell line for more than 7 days due to the presence of unpaired cysteines. The purified recombinant RBD yield from culture broth was 30–50 mg/L. Monomeric and homodimeric RBD forms were separated using gel-filtration chromatography and characterised by their ability to interact with specific monoclonal antibodies, as well as with serum samples from vaccinated volunteers. The homodimeric recombinant RBD showed increased avidity for both monoclonal and immune sera antibodies. Conclusions: the homodimeric recombinant RBD may be more preferable for the analysis of levels of antibodies to the receptor-binding domain of the SARS-CoV-2 S protein.

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“…Ozoralizumab and vobarilizumab are two other V H Hs currently utilised in clinical trials for rheumatoid arthritis [ 51 , 52 ]. Very recently, in the context of the COVID-19 pandemic, an impressive number of V H Hs have also been developed against the SARS-CoV-2 spike protein [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Therefore, a large number of pharmaceutical companies are now developing V H Hs.…”

Section: Introductionmentioning

confidence: 99%

VHH Structural Modelling Approaches: A Critical Review

Vishwakarma

Vattekatte

Shinada³

et al. 2022

IJMS

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VHH, i.e., VH domains of camelid single-chain antibodies, are very promising therapeutic agents due to their significant physicochemical advantages compared to classical mammalian antibodies. The number of experimentally solved VHH structures has significantly improved recently, which is of great help, because it offers the ability to directly work on 3D structures to humanise or improve them. Unfortunately, most VHHs do not have 3D structures. Thus, it is essential to find alternative ways to get structural information. The methods of structure prediction from the primary amino acid sequence appear essential to bypass this limitation. This review presents the most extensive overview of structure prediction methods applied for the 3D modelling of a given VHH sequence (a total of 21). Besides the historical overview, it aims at showing how model software programs have been shaping the structural predictions of VHHs. A brief explanation of each methodology is supplied, and pertinent examples of their usage are provided. Finally, we present a structure prediction case study of a recently solved VHH structure. According to some recent studies and the present analysis, AlphaFold 2 and NanoNet appear to be the best tools to predict a structural model of VHH from its sequence.

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Single-Domain Antibodies Efficiently Neutralize SARS-CoV-2 Variants of Concern

Cited by 28 publications

References 48 publications

rAAV expressing recombinant neutralizing antibody for the botulinum neurotoxin type A prophylaxis

rAAV expressing recombinant neutralizing antibody for the botulinum neurotoxin type A prophylaxis

Production and characterisation of a SARS-CoV-2 S-protein RBD homodimer with increased avidity for specific antibodies

VHH Structural Modelling Approaches: A Critical Review

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