Antibody landscape against SARS-CoV-2 reveals significant differences between non-structural/accessory and structural proteins

Yang, Li; Xu, Zhaowei; Lei, Qing; Lai, Dan‐yun; Hou, Hongyan; Jiang, He‐wei; Zheng, Yun-xiao; Wang, Xue-ning; Wu, Jiaoxiang; Ma, Ming‐liang; Zhang, Bo; Chen, Hong; Yu, Caizheng; Xue, Jun‐biao; Zhang, Hainan; Qi, Huan; Guo, Shujuan; Zhang, Yandi; Lin, Xiang; Yao, Zongjie; Sheng, Huiming; Sun, Ziyong; Fan, Xionglin; Tao, Sheng-Ce

doi:10.1016/j.celrep.2021.109391

Cited by 34 publications

(27 citation statements)

References 46 publications

(66 reference statements)

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“…Similarly, Lynch et al reported that the IgG and IgM levels against the RBD and N proteins were significantly higher in patients admitted to the intensive care units compared to those with a milder disease in all time intervals [ 17 ]. Li et al explored the IgG responses against various structural and non-structural SARS-CoV-2 antigens and found that the positivity rate and/or IgG levels against S1, NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b were significantly higher in patients with severe than non-severe disease [ 18 ]. From these non-structural proteins, only NSP1 and ORF3b were represented on our antigen array.…”

Section: Discussionmentioning

confidence: 99%

Early and strong antibody responses to SARS-CoV-2 predict disease severity in COVID-19 patients

et al. 2022

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Background Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown. Methods A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls. Results Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation. Conclusions This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.

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Section: Discussionmentioning

confidence: 99%

Early and strong antibody responses to SARS-CoV-2 predict disease severity in COVID-19 patients

et al. 2022

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“…Moreover, it should be considered that additional SARS-CoV-2 antigens, different from the “classic” Spike, Nucleoprotein and Membrane may be of importance to track SARS-CoV-2-specific memory durability. This is further supported by the recent identification of antibodies against non-structural/accessory proteins in COVID-19 patients, as well as of HLA-I peptides derived from both canonical open reading frames (ORFs) and internal out-of-frame ORFs of S and N proteins [ 230 , 217 ]. These data open the way to further investigation and strategic approach in monitoring SARS-CoV-2 specific immune response.…”

Section: Heterogeneous Adaptive Immune Response To Sars-cov-2mentioning

confidence: 96%

Hallmarks of immune response in COVID-19: Exploring dysregulation and exhaustion

Mazzoni

Salvati

Maggi

et al. 2021

Seminars in Immunology

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One and half year following the occurrence of COVID-19 pandemic, significant efforts from laboratories all over the world generated a huge amount of data describing the prototypical features of immunity in the course of SARS-CoV-2 infection. In this Review, we rationalize and organize the main observations, trying to define a “core” signature of immunity in COVID-19. We identified six hallmarks describing the main alterations occurring in the early infection phase and in the course of the disease, which predispose to severe illness. The six hallmarks are dysregulated type I IFN activity, hyperinflammation, lymphopenia, lymphocyte impairment, dysregulated myeloid response, and heterogeneous adaptive immunity to SARS-CoV-2. Dysregulation and exhaustion came out as the trait d’union, connecting abnormalities affecting both innate and adaptive immunity, humoral and cellular responses.

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“…To further confirm the applicability of the protein microarray, 14 convalescent sera (Table S1-cohort 1) were analyzed following an established protocol 6,7 , besides IgG, IgM and IgA responses were also compared between RBD-WT and RBD-Omicron. Significantly lower signals were observed for all these 3 types of antibodies against RBD-Omicron, specifically, 3.44x, 8.71 and 4.26x for IgG, IgM and IgA, respectively.…”

Section: The Omicron Rbd Protein Microarraymentioning

confidence: 99%

One year landscape of the inactivated virus vaccine triggered RBD-specific IgG, IgM and IgA responses against the Omicron variant

Xue

Lai

Jiang

et al. 2022

Preprint

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We reported the first map of vaccine stimulated RBD-specific antibody responses (IgG, IgM and IgA) against the Omicron variant. We generated the map using a protein microarray, by analyzing longitudinal sera collected spanning one year from individuals immunized with 3 doses of an inactivated virus vaccine. The IgG response to RBD-Omicron is: 1/3-1/5 that of RBD-wild type; ~6x higher for the booster dose vs. the 2nd dose; and reaches the plateau in about two weeks after the booster dose, then drops ~5x in another two weeks. Similar results were also obtained for IgM and IgA. Because of the high correlation between RBD-specific antibody response and the neutralization activity to authentic virus, we at least indirectly revealed the landscape of antibody protection against the Omicron variant throughout the vaccination stages. Our results strongly support the necessity of booster vaccination. However, post-booster vaccination may need to be considered.

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Antibody landscape against SARS-CoV-2 reveals significant differences between non-structural/accessory and structural proteins

Cited by 34 publications

References 46 publications

Early and strong antibody responses to SARS-CoV-2 predict disease severity in COVID-19 patients

Early and strong antibody responses to SARS-CoV-2 predict disease severity in COVID-19 patients

Hallmarks of immune response in COVID-19: Exploring dysregulation and exhaustion

One year landscape of the inactivated virus vaccine triggered RBD-specific IgG, IgM and IgA responses against the Omicron variant

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