B cell memory: building two walls of protection against pathogens

Akkaya, Munir; Kwak, Kihyuck

doi:10.1038/s41577-019-0244-2

Cited by 356 publications

(319 citation statements)

References 80 publications

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“…These patients were the earliest confirmed cases of SARS-CoV-2 infection in Chongqing City, over half of the patients who had a history of close contact with the earliest infectors. Antigen specific B cells from memory B cells experienced affinity maturation and somatic hypermutation 24,25 . Thus, RBD specific memory B cells in these patients were potentially useful candidates to screen out the potent neutralizing Abs.…”

Section: Resultsmentioning

confidence: 99%

A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

Han

Wang

et al. 2020

Preprint

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Neutralizing antibodies (Abs) have been considered as promising therapeutics for the prevention and treatment of pathogens. After the outbreak of COVID-19, potent neutralizing Abs to SARS-CoV-2 were promptly developed, and a few of those neutralizing Abs are being tested in clinical studies. However, there were few methodologies detailly reported on how to rapidly and efficiently generate neutralizing Abs of interest. Here, we present a strategically optimized method for precisive screening of neutralizing monoclonal antibodies (mAbs), which enabled us to identify SARS-CoV-2 receptor-binding domain (RBD) specific Abs within 4 days, followed by another 2 days for neutralization activity evaluation. By applying the screening system, we obtained 198 Abs against the RBD of SARS-CoV-2. Excitingly, we found that approximately 50% (96/198) of them were candidate neutralizing Abs in a preliminary screening of SARS-CoV-2 pseudovirus and 20 of these 96 neutralizing Abs were confirmed with high potency. Furthermore, 2 mAbs with the highest neutralizing potency were identified to block authentic SARS-CoV-2 with the half-maximal inhibitory concentration (IC50) at concentrations of 9.88 ng/ml and 11.13 ng/ml. In this report, we demonstrated that the optimized neutralizing Abs screening system is useful for the rapid and efficient discovery of potent neutralizing Abs against SARS-CoV-2. Our study provides a methodology for the generation of preventive and therapeutic antibody drugs for emerging infectious diseases.

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Section: Resultsmentioning

confidence: 99%

A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

Han

Wang

et al. 2020

Preprint

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“…2). Firstly, we utilized the RBD of SARS-CoV-2 as bait to label specific mB cells, which would usually experience affinity maturation and somatic hypermutation 32,33 . SARS-CoV-2 RBD has been proven to be essential for the ACE2-binding during virus entry 8 .…”

Section: Discussionmentioning

confidence: 99%

A rapid and efficient screening system for neutralizing antibodies and its application for SARS-CoV-2

Han

Wang

et al. 2020

Preprint

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After the epidemic of COVID-19, neutralizing antibodies (NAbs) against SARS-CoV-2 has been developed for the preventative and therapeutic purposes. However, few methodologies are reported in detail on how to rapidly and efficiently generate NAbs of interest. Here, we present a strategically optimized screening method for NAbs, which has enabled us to obtain SARS-CoV-2 receptor-binding domain (RBD) specific monoclonal Abs within 4 days, followed by additional 2 days to evaluate their neutralizing activities. Using this method, we obtained 198 specific Abs against SARS-CoV-2 RBD from the blood samples of COVID-19 convalescent patients, and 96 of them showed neutralizing activity. At least 20% of these NAbs exhibited high neutralizing potency. The top 2 NAbs showed the half-maximal inhibitory concentration (IC50) to block authentic SARS-CoV-2 at 9.88 and 11.13 ng/ml, respectively. Altogether, our study provides a fundamental methodology for discovering NAbs with potential preventative and therapeutic value for emerging infectious diseases.

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“…Among them, the in ammatory cytokines are mainly TNF, IL-6, IL-1β, CCL2, IL-10, IL-2, which concentrate on in ammatory responses. As reported, IL-6 is an important cytokine that initially expressed through the immune system in response to injurious or infectious processes(17) [17]. In the early stage, it activates the JAK/STAT signal pathway, and initiates B cell differentiation, plasma cell production and a series of acute reactions (18,19) [18,19].…”

Section: Discussionmentioning

confidence: 97%

Uncovering the underlying mechanisms of Compound Yuxingcao Mixture in the treatment of COVID-19 based on network pharmacology

Chen¹,

Zhang²,

Yuan³

et al. 2020

Preprint

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Background and objective: The novel coronavirus named COVID-19 emerged in Wuhan, China in December, 2019 and has spread rapidly in China and around the world. The traditional Chinese medicine Compound Yuxingcao Mixture (CYM) has been recommended in recent editions of the national guideline while the underlying mechanisms are still unclear. In this study, we analyzed the effectiveness and potential mechanisms of CYM on COVID-19 based on network pharmacology and molecular docking approach. Methods: The active ingredients and potential targets of CYM were screened using TCMSP and STITCH databases. Genes related severe acute respiratory syndromes (SARS) and Middle East respiratory syndrome (MERS) were queried on the DisGeNET and MalaCards databases. CYM-COVID-19 common target protein interaction network was established by STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to generate the relative pathways based on KOBAS databases. In addition, the possible binding site of screened compounds were also predicted by Autodock vina software. Results: A total of 103 active ingredients and 205 putative targets were screened from CYM, of which 32 overlapped with the targets of COVID-19 and were considered therapeutic targets. The analysis of the network diagram demonstrated that the CYM activity of ingredients of quercetin, luteolin, β-sitosterol and kaempferol may play a crucial role in treating COVID-19 by regulating TNF, IL-6, IL-1β, etc. The analysis of molecular binding energy showed that β-sitosterol had the lowest binding energy with COVID-19 3CLpro (-8.63 kJ/mol). GO and KEGG enrichment analysis revealed that these targets were closely associated with inflammatory responses and immune defense processes. Conclusion: In summary, our study identified the potential mechanisms and targets of CYM for the prevention of COVID-19, providing directions for further clinical research.

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B cell memory: building two walls of protection against pathogens

Cited by 356 publications

References 80 publications

A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

A rapid and efficient screening system for neutralizing antibodies and its application for SARS-CoV-2

Uncovering the underlying mechanisms of Compound Yuxingcao Mixture in the treatment of COVID-19 based on network pharmacology

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