SARS-CoV2 envelop proteins reshape the serological responses of COVID-19 patients

Martin, Sophie; Heslan, Christopher; Jégou, Gwénaële; Eriksson, Leif A.; Gallo, Matthieu Le; Thibault, Vincent; Chevet, Éric; Godey, Florence; Avril, Tony

doi:10.1101/2021.02.15.431237

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…Consistent with the results presented here, a recent study investigating serum reactivity to the structural proteins of SARS-CoV-2 by flow cytometry also found a high prevalence of M antibodies in COVID-19 positive patient sera, although only approximately 50% of COVID-19 patients tested contained M antibodies (Martin 2021).…”

Section: Discussionsupporting

confidence: 91%

A high content microscopy-based platform for detecting antibodies to the nucleocapsid, spike and membrane proteins of SARS-CoV-2

Williams

Hornsby

Shehata

et al. 2021

Preprint

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The strong humoral immune response produced against the SARS-CoV-2 nucleocapsid (N) and spike (S) proteins has underpinned serological testing but the prevalence of antibody responses to other SARS-CoV-2 proteins, which may be of use as further serological markers, is still unclear. Cell-based serological screening platforms can fulfil a crucial niche in the identification of antibodies which recognise more complex folded epitopes or those incorporating post-translation modifications which may be undetectable by other methods used to investigate the antigenicity of the SARS-CoV-2 proteome. Here, we employed automated high content immunofluorescence microscopy (AHCIM) to assess the viability of such an approach as a method capable of assaying humoral immune responses against full length SARS-CoV-2 proteins in their native cellular state. We first demonstrate that AHCIM provides high sensitivity and specificity in the detection of SARS-CoV-2 N and S IgG. Assessing the prevalence of antibody responses to the SARS-CoV-2 structural membrane protein (M), we further find that 85% of COVID-19 patients within our sample set developed detectable M IgG responses (M sensitivity 85%, N sensitivity 93%, combined N + M sensitivity 95%). The identification of M as a serological marker of high prevalence may be of value in detecting additional COVID-19 cases during the era of mass SARS-CoV-2 vaccinations, where serological screening for SARS CoV-2 infections in vaccinated individuals is dependent on detection of antibodies against N. These findings highlight the advantages of using cell-based systems as serological screening platforms and raise the possibility of using M as a widespread serological marker alongside N and S.

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Section: Discussionsupporting

confidence: 91%

A high content microscopy-based platform for detecting antibodies to the nucleocapsid, spike and membrane proteins of SARS-CoV-2

Williams

Hornsby

Shehata

et al. 2021

Preprint

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“…The correlation between complement component C1q and MBL with the immunogenicity via the activation of the complement system has been discussed above. For integral membrane protein 2B, a recent serological study demonstrated that the antibodies produced by COVID-19 patients showed an unexpected immune response against integral membrane proteins, which can be used to detect SARS-CoV-2 variants or test vaccine effectiveness (59). We found that integral membrane protein 2B was less abundant in the NAbs positive individuals.…”

Section: Discussionmentioning

confidence: 70%

Serum peptidome profiles immune response of COVID-19 Vaccine administration

Zhang

Li²,

Xu³

et al. 2022

Front. Immunol.

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BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant loss of life and property. In response to the serious pandemic, recently developed vaccines against SARS-CoV-2 have been administrated to the public. Nevertheless, the research on human immunization response against COVID-19 vaccines is insufficient. Although much information associated with vaccine efficacy, safety and immunogenicity has been reported by pharmaceutical companies based on laboratory studies and clinical trials, vaccine evaluation needs to be extended further to better understand the effect of COVID-19 vaccines on human beings.MethodsWe performed a comparative peptidome analysis on serum samples from 95 participants collected at four time points before and after receiving CoronaVac. The collected serum samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to profile the serum peptides, and also subjected to humoral and cellular immune response analyses to obtain typical immunogenicity information.ResultsSignificant difference in serum peptidome profiles by MALDI-TOF MS was observed after vaccination. By supervised statistical analysis, a total of 13 serum MALDI-TOF MS feature peaks were obtained on day 28 and day 42 of vaccination. The feature peaks were identified as component C1q receptor, CD59 glycoprotein, mannose-binding protein C, platelet basic protein, CD99 antigen, Leucine-rich alpha-2-glycoprotein, integral membrane protein 2B, platelet factor 4 and hemoglobin subunits. Combining with immunogenicity analysis, the study provided evidence for the humoral and cellular immune responses activated by CoronaVac. Furthermore, we found that it is possible to distinguish neutralizing antibody (NAbs)-positive from NAbs-negative individuals after complete vaccination using the serum peptidome profiles by MALDI-TOF MS together with machine learning methods, including random forest (RF), partial least squares-discriminant analysis (PLS-DA), linear support vector machine (SVM) and logistic regression (LR).ConclusionsThe study shows the promise of MALDI-TOF MS-based serum peptidome analysis for the assessment of immune responses activated by COVID-19 vaccination, and discovered a panel of serum peptides biomarkers for COVID-19 vaccination and for NAbs generation. The method developed in this study can help not only in the development of new vaccines, but also in the post-marketing evaluation of developed vaccines.

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“…Some of the latter appear to be shared with common non-SARS-CoV-2 coronaviruses [34,45]. For unknown reasons, the Envelope (E) protein which is virus surface-exposed does not attract humoral immune reactivity very well [46]. Antigen-specific antibody responses can vary, and stereotypic de novo responses occur [34,35,37,[47][48][49].…”

Section: Immunogens and Humoral Immunitymentioning

confidence: 99%

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Cimolai¹

2021

CHI

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In the absence of effective antiviral chemotherapy and still in the context of emerging vaccines for severe acute respiratory syndrome-CoV-2 infections, passive immunotherapy remains a key treatment and possible prevention strategy. What might initially be conceived as a simplified donor-recipient process, the intricacies of donor plasma, IV immunoglobulins, and monoclonal antibody modality applications are becoming more apparent. Key targets of such treatment have largely focused on virus neutralization and the specific viral components of the attachment Spike protein and its constituents (e.g., receptor binding domain, N-terminal domain). The cumulative laboratory and clinical experience suggests that beneficial protective and treatment outcomes are possible. Both a dose-and a time-dependency emerge. Lesser understood are the concepts of bioavailability and distribution. Apart from direct antigen binding from protective immunoglobulins, antibody effector functions have potential roles in outcome. In attempting to mimic the natural but variable response to infection or vaccination, a strong functional polyclonal approach attracts the potential benefits of attacking antigen diversity, high antibody avidity, antibody persistence, and protection against escape viral mutation. The availability and ease of administration for any passive immunotherapy product must be considered in the current climate of need. There is never a perfect product, but yet there is considerable room for improving patient outcomes. Given the variability of human genetics, immunity, and disease, and given the nuances of the virus and its potential for change, passive immunotherapy can be developed that will be effective for some but not all patients. An understanding of such patient variability and limitations is just as important as the understanding of the direct interactions between immunotherapy and virus.

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SARS-CoV2 envelop proteins reshape the serological responses of COVID-19 patients

Cited by 3 publications

References 46 publications

A high content microscopy-based platform for detecting antibodies to the nucleocapsid, spike and membrane proteins of SARS-CoV-2

A high content microscopy-based platform for detecting antibodies to the nucleocapsid, spike and membrane proteins of SARS-CoV-2

Serum peptidome profiles immune response of COVID-19 Vaccine administration

Passive Immunity Should and Will Work for COVID-19 for Some Patients

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