Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine

Kramer, Kevin J.; Wilfong, Erin M.; Voss, Kelsey; Barone, Sierra; Shiakolas, Andrea R; Raju, Nagarajan; Roe, Caroline E.; Suryadevara, Naveen Chandra; Walker, Lauren M.; Wall, Steven; Paulo, Ariana; Schaefer, Samuel; Dahunsi, Debolanle; Westlake, Camille S.; Crowe, James E.; Carnahan, Robert H.; Rathmell, Jeffrey C.; Bonami, Rachel H.; Georgiev, Ivelin S.; Irish, Jonathan M.

doi:10.1038/s41467-022-31142-5

Cited by 38 publications

(40 citation statements)

References 105 publications

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“…Both SARS-CoV-2 infection and vaccination effectively elicited T cell and B cell responses against SARS-CoV-2 (3,16), providing a high level of protection against symptomatic SARS-CoV-2 infection (17), despite the challenges posed to the waned immunity by the immunity-escaping emerging viral variants. Of note, single-cell analysis together with the classic immunological assay, have greatly contributed to deeper understanding of the dynamics of SARS-CoV-2-specific CD4 + and CD8 + T cells, B cells and neutralizing antibodies (18)(19)(20)(21)(22)(23) during natural infection and various vaccination (Table 1) (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). A comprehensive comparison of the adaptive immune responses with natural infection and vaccination is required to dissect the protective immune properties against SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Single-cell analysis of the adaptive immune response to SARS-CoV-2 infection and vaccination

Cao

Zhang

et al. 2022

Front. Immunol.

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Amid the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, vaccination and early therapeutic interventions are the most effective means to combat and control the severity of the disease. Host immune responses to SARS-CoV-2 and its variants, particularly adaptive immune responses, should be fully understood to develop improved strategies to implement these measures. Single-cell multi-omic technologies, including flow cytometry, single-cell transcriptomics, and single-cell T-cell receptor (TCR) and B-cell receptor (BCR) profiling, offer a better solution to examine the protective or pathological immune responses and molecular mechanisms associated with SARS-CoV-2 infection, thus providing crucial support for the development of vaccines and therapeutics for COVID-19. Recent reviews have revealed the overall immune landscape of natural SARS-CoV-2 infection, and this review will focus on adaptive immune responses (including T cells and B cells) to SARS-CoV-2 revealed by single-cell multi-omics technologies. In addition, we explore how the single-cell analyses disclose the critical components of immune protection and pathogenesis during SARS-CoV-2 infection through the comparison between the adaptive immune responses induced by natural infection and by vaccination.

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Section: Introductionmentioning

confidence: 99%

Single-cell analysis of the adaptive immune response to SARS-CoV-2 infection and vaccination

Cao

Zhang

et al. 2022

Front. Immunol.

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“…demonstrated increasing spike-specific B cells, antigen-specific CD4 + T cells, and CD8 + T cells by scRNA-seq analysis in healthy subjects after mRNA vaccines and those after COVID-19 infection ( 31 ). Kramer KJ and the colleagues focused on adaptive immunity and indicated enlarged population of antigen-specific memory CD4+ and CD8+ T cells, and IgA and IgG memory B cells specific to SARS-CoV-2 in healthy participants after BNT162b2 mRNA vaccines ( 32 ). Those studies highlighted the importance of antigen presentation and antibodies productions following mRNA vaccines in healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases

et al. 2022

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ObjectivesTo investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group.ConclusionsmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

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“… 264 , 265 A mass cytometry‐based study identified expansion of metabolically active, class‐switched plasmablasts expressing CD71, CD98, and cytochrome C between day 0 and 28 post‐vaccine. 266 Similarly, Amanat et al 128 reported that some of the isolated S2‐specific mAbs had cross‐reactivity toward human coronaviruses, suggestive of recall responses which were initially induced by seasonal beta‐coronavirus exposure. To support this model, some of the cross‐reactive mAbs showed extensive SHM.…”

Section: Asc Responses To Sars‐cov ‐2 Vac...mentioning

confidence: 99%

“…Studies have shown that the first dose generated polyclonal non‐neutralizing IgA‐dominant ASC response with some S2‐specific plasmablasts with low SHM, whereas the second dose provided neutralizing B cell responses to S1 with RBD 264,265 . A mass cytometry‐based study identified expansion of metabolically active, class‐switched plasmablasts expressing CD71, CD98, and cytochrome C between day 0 and 28 post‐vaccine 266 . Similarly, Amanat et al 128 reported that some of the isolated S2‐specific mAbs had cross‐reactivity toward human coronaviruses, suggestive of recall responses which were initially induced by seasonal beta‐coronavirus exposure.…”

Section: Asc Responses To Sars‐cov‐2 Vaccinationmentioning

confidence: 99%

COVID‐19 and plasma cells: Is there long‐lived protection?*

Nguyen

Lamothe

Woodruff

et al. 2022

Immunological Reviews

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The SARS-CoV-2 pandemic arose in China at the end of 2019 and has caused over 450 million infections and more than 6 million deaths worldwide. Initially, the virus caused a wide range of clinical manifestations from asymptomatic and mild to severe and critical, leading to death in ~1.5% of infected individuals. Elderly patients were initially at risk of severe disease together with those who had co-morbid conditions, such as diabetes and obesity. Pneumonia and respiratory failure often led to hospitalization; however, this infection caused gastrointestinal and endothelial injury leading to systemic illness affecting multiple organ systems that included the brain and many others. 1 With mild illness even after recovery, post-acute sequelae of SARS-CoV-2 infection (PASC) has also been reported without clear underlying pathophysiologic mechanisms. 2 At first, sequelae were thought to occur only after severe infection, but now PASC has been commonly reported after

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Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine

Cited by 38 publications

References 105 publications

Single-cell analysis of the adaptive immune response to SARS-CoV-2 infection and vaccination

Single-cell analysis of the adaptive immune response to SARS-CoV-2 infection and vaccination

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases

COVID‐19 and plasma cells: Is there long‐lived protection?*

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