Dissecting antibody-mediated protection against SARS-CoV-2

Zohar, Tomer; Alter, Galit

doi:10.1038/s41577-020-0359-5

Cited by 225 publications

(256 citation statements)

References 9 publications

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“…Understanding the antibody response and potential immunity to SARS-CoV-2 is critical for global public health and the development of efficacious vaccines 1,3, 26 . In this study, we performed a comprehensive analysis of the SARS-CoV-2-specific antibody response in 101 convalescent healthcare workers serum samples.…”

Section: Discussionmentioning

confidence: 99%

High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

Noval

Rodriguez-Rodriguez

Louie

et al. 2020

Preprint

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Understanding antibody responses to SARS-CoV-2 is indispensable for the development of containment measures to overcome the current COVID-19 pandemic. Here, we determine the ability of sera from 101 recovered healthcare workers to neutralize both authentic SARS-CoV-2 and SARS-CoV-2 pseudotyped virus and address their antibody titers against SARS-CoV-2 nucleoprotein and spike receptor-binding domain. Interestingly, the majority of individuals have low neutralization capacity and only 6% of the healthcare workers showed high neutralizing titers against both authentic SARS-CoV-2 virus and the pseudotyped virus. We found the antibody response to SARS-CoV-2 infection generates antigen-specific isotypes as well as a diverse combination of antibody isotypes, with high titers of IgG, IgM and IgA against both antigens correlating with neutralization capacity. Importantly, we found that neutralization correlated with antibody titers as quantified by ELISA. This suggests that an ELISA assay can be used to determine seroneutralization potential. Altogether, our work provides a snapshot of the SARS-CoV-2 neutralizing antibody response in recovered healthcare workers and provides evidence that possessing multiple antibody isotypes may play an important role in SARS-CoV-2 neutralization.

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Section: Discussionmentioning

confidence: 99%

High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

Noval

Rodriguez-Rodriguez

Louie

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Decreased IgG fucosylation, as observed in severe cases of COVID-19, has so far only been observed in patients infected with HIV and Dengue virus (33,34), but may actually be a general phenomenon in a response to enveloped viruses (26). While decreased fucosylation increases the infection of cells by a process known as antibody-dependent enhancement (ADE)(35), there is little evidence for antibody-enhanced infection in COVID-19 (36). Instead, our data show that increased pathology by de-fucosylated IgG in COVID-19 patients most likely results from excessive immune activation.…”

Section: Main Textmentioning

confidence: 99%

Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses

Hoepel

Chen

Allahverdiyeva

et al. 2020

Preprint

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For yet unknown reasons, severely ill COVID-19 patients often become critically ill around the time of activation of adaptive immunity. Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. The excessive inflammatory capacity of this anti-Spike IgG is related to glycosylation changes in the IgG Fc tail. Moreover, the hyper-inflammatory response induced by anti-Spike IgG can be specifically counteracted in vitro by use of the active component of fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk.One sentence summaryAnti-Spike IgG promotes hyper-inflammation.

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“…Most recently, investigations into COVID-19 convalescence individuals' sera have led to the identifications of highly potent neutralizing IgG antibodies (NAbs) primarily targeting the RBD but also non-RBD epitopes (7)(8)(9)(10)(11)(12)(13). Highquality NAbs may overcome the risks of the Fc-associated antibody-dependent enhancement (ADE) and are promising therapeutic and prophylactic candidates (14,15).…”

Section: Introductionmentioning

confidence: 99%

Versatile, Multivalent Nanobody Cocktails Efficiently Neutralize SARS-CoV-2

Xiang

Nambulli

Xiao

et al. 2020

Preprint

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The outbreak of COVID-19 has severely impacted global health and economy. Cost-effective therapeutics are urgently needed. Here, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the SARS-CoV-2 spike protein receptor-binding domain (RBD). We discovered multiple elite Nbs of picomolar to femtomolar affinities that inhibit viral infection at as low as sub-ng/ml concentration, more potent than some of the best human neutralizing antibodies. We then determined a crystal structure of such an elite neutralizing Nb in complex with RBD. Structural proteomics and integrative modeling revealed multiple distinct and non-overlapping epitopes and indicated an array of potential neutralization mechanisms. Structural characterization facilitated the bioengineering of novel multivalent Nb constructs into multi-epitope cocktails that achieved ultrahigh neutralization potency (IC50s as low as 0.058 ng/ml) and may prevent mutational escape. Our Nbs can be rapidly produced in bulk from microbes and resist heat, lyophilization, and aerosolization. These highly promising agents are readily translated into efficient, economic, and convenient therapeutics to help end this once-in-a-century health crisis.

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Dissecting antibody-mediated protection against SARS-CoV-2

Cited by 225 publications

References 9 publications

High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses

Versatile, Multivalent Nanobody Cocktails Efficiently Neutralize SARS-CoV-2

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