FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3202473359> ?p ?o ?g. }

• W3202473359 endingPage "e91" @default.
• W3202473359 startingPage "e90" @default.
• W3202473359 abstract "To The Editor: Understanding the composition and duration of immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is critical for prevention of infection. The most critical elements of immunity to SARS-CoV-2 are neutralizing antibody and T-cell immunity. Current assessments of immunity and risk for infections largely depended on detection of antibodies to SARS-CoV-2. However, taken alone, this represents an often-unreliable tool due to the evanescent nature of spike immunoglobulin G (IgG) responses.1-3 Here, an important and more durable response involves cytotoxic T-cells that can eliminate virally infected cells and T helper cells, which are critical to coordinating adaptive immunity toward the virus and generating long-lasting immunologic memory. However, T-cell responses are more difficult to assess. These issues become more prescient in determining immunity to SARS-CoV-2 in immunocompromised individuals where a majority show no IgG responses to vaccines and the recent emergence of the Delta variant with reports of >74% vaccine breakthrough cases.4,5 Here, we report on patients demonstrating divergent immune responses to SARS-CoV-2 vaccination. Institutional Review Board approval and informed consent was obtained before performance of assays (Appendix 1, SDC, https://links.lww.com/TP/C290). Seven patients were identified from a cohort of 70 immunocompromised patients, with all demonstrating spike-specific IgG unresponsiveness 2–4 mo postvaccination. All had received treatment with B-cell modifying agents. We subsequently examined CD4+/CD8+ T-cell–spike-specific immune responses in all patients and repeat examination after revaccination in 2 patients (see Appendix 1, SDC, https://links.lww.com/TP/C290, for Methods and Data). CD4+/CD8+ T-cell responses are shown in Figure 1 and demonstrate robust CD4+T-cell (0.94 ± 1.2%, Normal > 0.05%) and CD8+ T-cell (0.89 ± 1.2%, Normal > 0.05%) immune responses to spike peptides. Two patients receiving Johnson & Johnson booster vaccines demonstrated increased T-cell responses but remained spike IgG negative. This suggests that T-cell immune responses to SARS-CoV-2 vaccines are primal and retentive and that B-cell depletion before vaccine exposure prevents the cascade of progression of B-cell activation necessary for SARS-CoV-2 spike IgG production.FIGURE 1.: A, Detectable CD4+/CD8+ T-cell immune responses in vaccinated patients against SARS-CoV-2 spike peptides. Flow cytometry diagrams from 7 patients (P1–P7) assessed after 2 doses of Pfizer or Moderna vaccines. Cells were stimulated by SARS-CoV-2 spike peptides pool (PepMix SARS-CoV-2 [spike glycoprotein, JPT) for 9 h in vitro in the presence of Brefeldin A and anti-CD28/CD49d (BD Bioscience, San Jose, CA). Cells were stained for T-cell surface markers followed by fixation, permeabilization, and intracellular staining of cytokines (BD Bioscience, San Jose, CA). Activated CD4+ T cells (IL-2+TNFα+) and CD8+ T cells (IFNγ+TNFα+) are shown in the upper right-hand corner of each flow box. B, This figure shows immune responses to SARS-CoV-2 spike peptides in 2 patients who obtained external revaccination with the Johnson & Johnson vaccine. As in (A), percentages of activated CD4+ T cells (IL-2+TNFα+) and CD8+ T cells (IFNγ+TNFα+) in blood are shown after first vaccination (2 doses) and after third vaccination (booster). Activated CD4+ T cells (IL-2+TNFα+) and CD8+ T cells (IFNγ+TNFα+) are shown in the upper right-hand corner of each flow box. IFNγ, interferon γ; IL, interleukin; P, patient; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNFα, tumor necrosis factor α.Absence of IgG responses to SARS-CoV-2 suggests patients be considered “unvaccinated.” However, we show that patients treated with B-cell–modifying agents develop robust T-cell immune responses to SARS-CoV-2 without generating IgG responses. These observations should be considered in light of data presented by Peng et al showing robust CD4+/CD8+ T-cell responses to SARS-CoV-2 after infection. A critical observation was the diversity of T-cell responses that likely extend beyond the persistence of spike antibody. IgG is necessary for sterilizing immunity and T-cells cannot prevent infection as antigen presentation is required, but T-cell immunity can be at the ready for viral elimination. This may provide an inside track for rapid deployment of SARS-CoV-2 immunity, and although not preventing infection, could alter the severity and duration of SARS-CoV-2 disease.6 This is supported by data from Oberhardt et al7 who recently showed that vaccine-induced CD8+ T cells were the main mediators of protection after vaccination since they emerged before detection of neutralizing antibody and expanded after booster vaccination. Thus, detection of T-cell immune responses in patients failing to generate spike-specific IgG may aid in a more comprehensive assessment of immunity to SARS-CoV-2, identifying patients who would no longer be considered “unvaccinated” based on negative spike-specific IgG. This likely has relevance to patients receiving B-cell directed therapies for autoimmune and hematologic diseases. ACKNOWLEDGMENTS The authors would like to express our gratitude to the members of the Transplant Immunotherapy Program and the Transplant Immunology Laboratory at Cedars-Sinai Medical Center for their dedication to improving patient outcomes and safety during the coronavirus disease 2019 pandemic. We would also like to thank the patients who participated in this study by donating their blood for analysis of SARS-CoV-2 reactive T-cells." @default.
• W3202473359 created "2021-10-11" @default.
• W3202473359 creator A5016549211 @default.
• W3202473359 creator A5017255264 @default.
• W3202473359 creator A5020557161 @default.
• W3202473359 creator A5021567917 @default.
• W3202473359 creator A5036281463 @default.
• W3202473359 creator A5043310276 @default.
• W3202473359 creator A5044616722 @default.
• W3202473359 creator A5052340882 @default.
• W3202473359 creator A5058147404 @default.
• W3202473359 creator A5058974233 @default.
• W3202473359 creator A5067740422 @default.
• W3202473359 creator A5073508821 @default.
• W3202473359 creator A5076738806 @default.
• W3202473359 creator A5081218594 @default.
• W3202473359 date "2021-09-20" @default.
• W3202473359 modified "2023-10-16" @default.
• W3202473359 title "Divergent Immune Responses to SARS-CoV-2 Vaccines in Immunocompromised Patients" @default.
• W3202473359 cites W3082438395 @default.
• W3202473359 cites W3083285583 @default.
• W3202473359 cites W3126802289 @default.
• W3202473359 cites W3158948419 @default.
• W3202473359 cites W3168825791 @default.
• W3202473359 cites W3174497461 @default.
• W3202473359 cites W3183161080 @default.
• W3202473359 doi "https://doi.org/10.1097/tp.0000000000003957" @default.
• W3202473359 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34582140" @default.
• W3202473359 hasPublicationYear "2021" @default.
• W3202473359 type Work @default.
• W3202473359 sameAs 3202473359 @default.
• W3202473359 citedByCount "2" @default.
• W3202473359 countsByYear W32024733592022 @default.
• W3202473359 crossrefType "journal-article" @default.
• W3202473359 hasAuthorship W3202473359A5016549211 @default.
• W3202473359 hasAuthorship W3202473359A5017255264 @default.
• W3202473359 hasAuthorship W3202473359A5020557161 @default.
• W3202473359 hasAuthorship W3202473359A5021567917 @default.
• W3202473359 hasAuthorship W3202473359A5036281463 @default.
• W3202473359 hasAuthorship W3202473359A5043310276 @default.
• W3202473359 hasAuthorship W3202473359A5044616722 @default.
• W3202473359 hasAuthorship W3202473359A5052340882 @default.
• W3202473359 hasAuthorship W3202473359A5058147404 @default.
• W3202473359 hasAuthorship W3202473359A5058974233 @default.
• W3202473359 hasAuthorship W3202473359A5067740422 @default.
• W3202473359 hasAuthorship W3202473359A5073508821 @default.
• W3202473359 hasAuthorship W3202473359A5076738806 @default.
• W3202473359 hasAuthorship W3202473359A5081218594 @default.
• W3202473359 hasBestOaLocation W32024733591 @default.
• W3202473359 hasConcept C154317977 @default.
• W3202473359 hasConcept C159047783 @default.
• W3202473359 hasConcept C159654299 @default.
• W3202473359 hasConcept C167672396 @default.
• W3202473359 hasConcept C193419808 @default.
• W3202473359 hasConcept C202751555 @default.
• W3202473359 hasConcept C203014093 @default.
• W3202473359 hasConcept C22070199 @default.
• W3202473359 hasConcept C2776090121 @default.
• W3202473359 hasConcept C2779341262 @default.
• W3202473359 hasConcept C3017875465 @default.
• W3202473359 hasConcept C55493867 @default.
• W3202473359 hasConcept C71924100 @default.
• W3202473359 hasConcept C86803240 @default.
• W3202473359 hasConcept C8891405 @default.
• W3202473359 hasConceptScore W3202473359C154317977 @default.
• W3202473359 hasConceptScore W3202473359C159047783 @default.
• W3202473359 hasConceptScore W3202473359C159654299 @default.
• W3202473359 hasConceptScore W3202473359C167672396 @default.
• W3202473359 hasConceptScore W3202473359C193419808 @default.
• W3202473359 hasConceptScore W3202473359C202751555 @default.
• W3202473359 hasConceptScore W3202473359C203014093 @default.
• W3202473359 hasConceptScore W3202473359C22070199 @default.
• W3202473359 hasConceptScore W3202473359C2776090121 @default.
• W3202473359 hasConceptScore W3202473359C2779341262 @default.
• W3202473359 hasConceptScore W3202473359C3017875465 @default.
• W3202473359 hasConceptScore W3202473359C55493867 @default.
• W3202473359 hasConceptScore W3202473359C71924100 @default.
• W3202473359 hasConceptScore W3202473359C86803240 @default.
• W3202473359 hasConceptScore W3202473359C8891405 @default.
• W3202473359 hasIssue "1" @default.
• W3202473359 hasLocation W32024733591 @default.
• W3202473359 hasLocation W32024733592 @default.
• W3202473359 hasLocation W32024733593 @default.
• W3202473359 hasLocation W32024733594 @default.
• W3202473359 hasOpenAccess W3202473359 @default.
• W3202473359 hasPrimaryLocation W32024733591 @default.
• W3202473359 hasRelatedWork W2018916009 @default.
• W3202473359 hasRelatedWork W2031253481 @default.
• W3202473359 hasRelatedWork W2164219360 @default.
• W3202473359 hasRelatedWork W2306091347 @default.
• W3202473359 hasRelatedWork W2478580149 @default.
• W3202473359 hasRelatedWork W3032210197 @default.
• W3202473359 hasRelatedWork W4283821855 @default.
• W3202473359 hasRelatedWork W4307359803 @default.
• W3202473359 hasRelatedWork W4381570565 @default.
• W3202473359 hasRelatedWork W573847062 @default.
• W3202473359 hasVolume "106" @default.
• W3202473359 isParatext "false" @default.

• next