Evaluation of Cellular and Serological Responses to Acute SARS-CoV-2 Infection Demonstrates the Functional Importance of the Receptor-Binding Domain

Mantus, Grace; Nyhoff, Lindsay E.; Kauffman, Robert C.; Edara, Venkata Viswanadh; Lai, Lilin; Floyd, Katharine; Shi, Pei Yong; Menachery, Vineet D.; Edupuganti, Srilatha; Scherer, Erin M.; Kay, Ariel; McNair, Nina; Anderson, Evan J.; Rouphael, Nadine; Ahmed, Rafi; Suthar, Mehul S.; Wrammert, Jens

doi:10.4049/jimmunol.2001420

Cited by 9 publications

(13 citation statements)

References 45 publications

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“…We have recently reported that RBD-specific MBCs upregulate the activation marker CD71 during acute COVID-19. 4 To determine the duration of activation, we assessed CD71 expression in RBD-binding and non-RBD-binding MBCs following SARS-CoV-2 infection and vaccination (Figure 2). One to two months after infection, a significantly higher percentage of RBD-specific MBCs retained expression of CD71 compared with their non-RBD-binding counterparts (p < 0.0001).…”

Section: Rbd-specific Mbcs Exhibit Sustained Activation As Measured B...mentioning

confidence: 99%

“…1 In numerous study cohorts, overwhelming evidence has illustrated the importance of antibodies targeting the trimeric spike (S) protein on the viral surface, especially the receptor-binding domain (RBD), in controlling SARS-CoV-2 infections. [2][3][4][5][6] RBD-specific antibodies in circulation correlate strongly with viral neutralization across infection cohorts, 7,8 and monoclonal antibodies derived from RBD-specific memory B cells generated during infection have been consistently characterized as potent neutralizers with several either approved for use or currently in clinical trials for treatment of coronavirus disease 2019 (COVID-19). 3,[5][6][7] Given the clear importance of RBD-specific antibodies in the protective immune response to infection, eliciting a similar antibody repertoire through vaccination was hypothesized to provide comparable immunity.…”

Section: Introductionmentioning

confidence: 99%

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Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination

Mantus

Nyhoff

Edara

et al. 2022

Cell Reports Medicine

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Section: Rbd-specific Mbcs Exhibit Sustained Activation As Measured B...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination

Mantus

Nyhoff

Edara

et al. 2022

Cell Reports Medicine

Self Cite

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“…While analyzing RBD specific switched memory B cells, this also showed a similar pattern to antibodies in terms of isotype. RBD specific IgG memory B cells are dominated followed by IgA and then IgM type [ 36 ].…”

Section: B Cells Response During Covid-19 Infectionmentioning

confidence: 99%

Neutralizing antibody: a savior in the Covid-19 disease

Gupta

Jaiswal

2022

Mol Biol Rep

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Coronavirus outbreak was declared a pandemic by World Health Organization (WHO) in March 2020. The pandemic has led to a devastating loss of life. It has shown us how infectious diseases can cause human existence at stake, and community health is important. The spike protein is the most immunogenic component of the virus. Most vaccine development strategies have focused on the receptor-binding domain (RBD) in the spike protein because it is the most specific target site that recognizes and interacts with human lung cells. Neutralizing antibodies are generated by the humoral immune system and reduce the viral load by binding to spike protein components. Neutralizing antibodies are the proteins secreted by plasma cells and serve as an important part of the defense mechanism. In the recent Covid-19 infection, neutralizing antibodies can be utilized for both diagnostic such as immune surveillance and therapeutic tools such as plasma therapy. So far, many monoclonal antibodies are in the clinical trial phase, and few of them are already in use. In this review, we have discussed details about neutralizing antibodies and their role in combating Covid-19 disease. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-021-07020-6.

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“…Both antigen targets were used previously for evaluating prior infection with SARS-CoV-2 on the basis of serum antibody reactivity [74,75]. Additionally, serum antibody reactivity against the RBD protein is a strong predictor of neutralizing activity [75,76]. As shown in Figure 1A, direct capture of the RBD protein at 10 µg/mL to the assay membrane failed to yield bright and welldefined IgG + FluoroSpots following overnight incubation of pre-stimulated PBMC from four recovered COVID-19 donors.…”

Section: Affinity Tag Capture Of Sars-cov-2 Spike Proteins Improves Antigen-specific Fluorospot Assaysmentioning

confidence: 99%

Affinity Tag Coating Enables Reliable Detection of Antigen-Specific B Cells in Immunospot Assays

Köppert

Wolf

Becza³

et al. 2021

Cells

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Assessment of humoral immunity to SARS-CoV-2 and other infectious agents is typically restricted to detecting antigen-specific antibodies in the serum. Rarely does immune monitoring entail assessment of the memory B-cell compartment itself, although it is these cells that engage in secondary antibody responses capable of mediating immune protection when pre-existing antibodies fail to prevent re-infection. There are few techniques that are capable of detecting rare antigen-specific B cells while also providing information regarding their relative abundance, class/subclass usage and functional affinity. In theory, the ELISPOT/FluoroSpot (collectively ImmunoSpot) assay platform is ideally suited for antigen-specific B-cell assessments since it provides this information at single-cell resolution for individual antibody-secreting cells (ASC). Here, we tested the hypothesis that antigen-coating efficiency could be universally improved across a diverse set of viral antigens if the standard direct (non-specific, low affinity) antigen absorption to the membrane was substituted by high-affinity capture. Specifically, we report an enhancement in assay sensitivity and a reduction in required protein concentrations through the capture of recombinant proteins via their encoded hexahistidine (6XHis) affinity tag. Affinity tag antigen coating enabled detection of SARS-CoV-2 Spike receptor binding domain (RBD)-reactive ASC, and also significantly improved assay performance using additional control antigens. Collectively, establishment of a universal antigen-coating approach streamlines characterization of the memory B-cell compartment after SARS-CoV-2 infection or COVID-19 vaccinations, and facilitates high-throughput immune-monitoring efforts of large donor cohorts in general.

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Evaluation of Cellular and Serological Responses to Acute SARS-CoV-2 Infection Demonstrates the Functional Importance of the Receptor-Binding Domain

Abstract: This information is current as the Receptor-Binding Domain Demonstrates the Functional Importance of Responses to Acute SARS-CoV-2 Infection Evaluation of Cellular and Serological

Cited by 9 publications

References 45 publications

Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination

Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination

Neutralizing antibody: a savior in the Covid-19 disease

Affinity Tag Coating Enables Reliable Detection of Antigen-Specific B Cells in Immunospot Assays

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