Neutralizing Antibody Responses to SARS-CoV-2 in a COVID-19 Recovered Patient Cohort and Their Implications

Wu, Fan; Wang, Aojie; Liu, Mei; Wang, Qimin; Chen, Jun; Xia, Shuai; Ling, Yun; Zhang, Yuling; Xun, Jingna; Lu, Lu; Jiang, Shibo; Lu, Hongzhou; Wen, Yumei; Huang, Jianhang

doi:10.2139/ssrn.3566211

Cited by 344 publications

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“…We found that epitopes/protein-specific antibody titres exceeded the microneutralisation titres by several orders of magnitude. Considering the relatively low neutralising antibody levels in the recovered patients in this study and in a previous report 26 , it is reasonable to expect significant differences between specific antibodies and neutralising antibodies. We found there was equivalent antiviral activity from immunisation with epitopes compared to immunisation with the entire RBD fragment (Figure 4).…”

Section: Discussionsupporting

confidence: 52%

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Zhang

Chen

et al. 2020

Preprint

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24The ongoing coronavirus disease 2019 pandemic is a serious threat to 25 global public health, and imposes severe burdens on the entire human society. The 26 severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can cause 27 severe respiratory illness and death. Currently, there are no specific antiviral drugs 28 that can treat COVID-19. Several vaccines against SARS-CoV-2 are being actively 29 developed by research groups around the world. The surface S (spike) protein and the 30 highly expressed internal N (nucleocapsid) protein of SARS-CoV-2 are widely 31 considered as promising candidates for vaccines. In order to guide the design of an 32 effective vaccine, we need experimental data on these potential epitope candidates. In 33 this study, we mapped the immunodominant (ID) sites of S protein using sera samples 34 collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-35 specific antibody levels in the sera of recovered COVID-19 patients were strongly 36 correlated with the neutralising antibody titres. We used epitope mapping to 37 determine the landscape of ID sites of S protein, which identified nine linearized B 38 cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain 39 (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-40 CoV-2 antibody binding sites. Peptides containing two out of the nine sites were 41 tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected 42 epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised 43 mice. This study for the first time provides human serological data for the design of 44 vaccines against COVID-19.45 46 47 The coronavirus disease 2019 (COVID-19), a novel infectious disease caused by 48 severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, first emerged in 49 December 2019 and has since become a worldwide pandemic. COVID-19 infections 50 have so far led to over 2 million cases and more than 0.13 million deaths across more 51 than 200 countries and geographical regions around the world. The World Health 52 Organization has launched a worldwide clinical trial called SOLIDARITY to test 53 antiviral treatment options for the novel coronavirus, but as of April 15, 2020, there 54 are no specific drugs for treating COVID-19 1 . Many research teams worldwide are 55 racing to develop vaccines against SARS-CoV-2 to combat this novel coronavirus 56 pandemic. 57 Similar to other coronaviruses, SARS-CoV-2 is an enveloped positive-stranded RNA 58 virus with four major structural proteins: S (spike), E (envelope), M (membrane), and 59 N (nucleocapsid) proteins 2-4 . The surface S protein is the key that allows SARS-COV-60 2 to enter into cells 5 , as it plays a role in binding to the cellular receptor and 61 membrane fusion 5,6 . The SARS-CoV-2 shares 75.96% homology with the 2003 62 SARS-CoV 3 , and the structure and functional domains of the SARS-CoV-2 S protein 63 have already been identified 7 . The receptor-binding domain...

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Section: Discussionsupporting

confidence: 52%

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Zhang

Chen

et al. 2020

Preprint

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“…Of note, even if tests are highly accurate, much about protective immunity is unknown and the true presence of binding antibodies might not mean that people have indeed developed high titers of neutralizing antibodies and are thus immune to re-infection 70 . Research on Rhesus macaques infected with SARS-CoV-2 was promising though showing that reinfection did not occur following rechallenge with the same dose of SARS-CoV-2 strain 71 .…”

Section: Discussionmentioning

confidence: 99%

Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

Kontou

Braliou

Dimou

et al. 2020

Preprint

124

129

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With the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography. In total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%. ELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies.

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“…On the other hand, ADE may affect safety and efficacy of passive and active immunisation schedules. A recent work reported the development of neutralising antibodies in most patients recovered from mild COVID-19 [27]: since patients with progression to a severe course were not studied, it was impossible to establish an association between this humoral response and disease. The authors cautioned that the variability of neutralising antibody development may raise a concern about their role on disease progression.…”

Section: Is There a Role For Ade In Covid-19?mentioning

confidence: 99%

Is antibody-dependent enhancement playing a role in COVID-19 pathogenesis?

Negro

2020

Swiss Med Wkly

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Neutralizing Antibody Responses to SARS-CoV-2 in a COVID-19 Recovered Patient Cohort and Their Implications

Cited by 344 publications

References 0 publications

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

Is antibody-dependent enhancement playing a role in COVID-19 pathogenesis?

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