Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients

Kreer, Christoph; Zehner, Matthias; Weber, Timm; Rohde, Cornelius; Halwe, Sandro; Ercanoglu, Meryem S.; Gieselmann, Lutz; Korenkov, Michael; Gruell, Henning; Schommers, Philipp; Vanshylla, Kanika; Cristanziano, Veronica Di; Janicki, Hanna; Brinker, Reinhild; Ashurov, Artem; Krähling, Verena; Kupke, Alexandra; Cohen-Dvashi, Hadas; Koch, Manuel; Lederer, Simone; Pfeifer, Nico; Wolf, Timo; Vehreschild, Maria J.G.T.; Wendtner, Clemens; Diskin, Ron; Becker, Stephan; Klein, Florian

doi:10.1101/2020.06.12.146290

Cited by 110 publications

(182 citation statements)

References 42 publications

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“…We showed RBD-SpyVLPs to be strongly immunogenic in mice and pigs, inducing high titre neutralising antibody responses against wild type SARS-CoV-2 virus. This study confirms that the RBD is the key immunogenic domain for eliciting neutralising monoclonal antibodies against SARS-CoV-2, in line with studies showing that highly neutralising antibodies isolated from convalescent patients bind to the RBD 16,26,38,[40][41][42][43][44][45][46] . We showed that RBD-SpyVLPs are recognised by a panel of mAbs isolated from convalescent patients 26 binding to various epitopes on the RBD (Figure 2A).…”

Section: Discussionsupporting

confidence: 84%

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Tan

Rijal

Rahikainen

et al. 2020

Preprint

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There is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle vaccine candidate displaying the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in a prime-boost regimen induced a strong neutralising antibody response in mice and pigs that was superior to convalescent human sera. We evaluated antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we showed that RBD-SpyVLP induced a polyclonal antibody response that recognised all key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. The induction of potent and polyclonal antibody responses by RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Moreover, RBD-SpyVLP is highly resilient, thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence.

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Section: Discussionsupporting

confidence: 84%

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Tan

Rijal

Rahikainen

et al. 2020

Preprint

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“…Neutralizing antibodies were considered as an ideal medicine for prophylaxis and treatment of infectious diseases 33 . At present, several potent neutralizing Abs to SARS-CoV-2 have been promptly developed and being tested in clinical trials (clinicaltrials.gov NCT04497987, NCT04426695 and NCT04425629) for treating COVID-19 patients [12][13][14][15]17,[19][20][21]34,35 . These reports showed that even though neutralizing antibodies against SASR-CoV-2 could be obtained from convalescent patients, the success rate to discover potent neutralizing antibodies with therapeutic value remains unideal.…”

Section: Discussionmentioning

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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“…Recent studies have shown that related, potently neutralizing monoclonal antibodies that recognize the SARS-CoV-2 receptor binding domain (RBD) are often elicited in SARS-CoV-2 infection (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). These antibodies have great potential to be clinically impactful in the treatment and prevention of SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

Weisblum

Schmidt

Zhang

et al. 2020

Preprint

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Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

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Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients

Cited by 110 publications

References 42 publications

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

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

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

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