Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection

Rezahosseini, Omid; Hamm, Sebastian Rask; Heftdal, Line Dam; Pérez‐Alós, Laura; Perch, Michael; Madsen, Johannes Roth; Hald, Annemette; Hansen, Cecilie Bo; Armenteros, José Juan Almagro; Pries-Heje, Mia Marie; Hasselbalch, Rasmus Bo; Fogh, Kamille; Frikke‐Schmidt, Ruth; Hilsted, Linda; Sørensen, Erik; Ostrowski, Sisse Rye; Harboe, Zitta Barrella; Iversen, Kasper; Bundgaard, Henning; Sørensen, Søren Schwartz; Rasmussen, Allan; Garred, Peter; Nielsen, Susanne Dam

doi:10.3389/fimmu.2022.1075423

Cited by 9 publications

(14 citation statements)

References 76 publications

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“…As SARS-CoV-2 variants continue to evolve, understanding vaccine immunogenicity in vulnerable populations is critical to informing vaccination strategies. SOTRs show impaired humoral and cellular responses to mRNA vaccines, 5,9,29,49 corresponding with increased susceptibility to SARS-CoV-2 infection. 4,25 In the present study, we have provided the first AIM-based characterization of COVID-19 vaccine-induced T cell responses to BA.4/5 and XBB.1.5 in SOTRs.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Variants Omicron BA.4/5 and XBB.1.5 Significantly Escape T Cell Recognition in Solid-organ Transplant Recipients Vaccinated Against the Ancestral Strain

Halvorson,

Ivison,

Huang

et al. 2023

Transplantation

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Background. Immune-suppressed solid-organ transplant recipients (SOTRs) display impaired humoral responses to COVID-19 vaccination, but T cell responses are incompletely understood. SARS-CoV-2 variants Omicron BA.4/5 (BA.4/5) and XBB.1.5 escape neutralization by antibodies induced by vaccination or infection with earlier strains, but T cell recognition of these lineages in SOTRs is unclear. Methods. We characterized Spike-specific T cell responses to ancestral SARS-CoV-2 and BA.4/5 peptides in 42 kidney, liver, and lung transplant recipients throughout a 3- or 4-dose ancestral Spike mRNA vaccination schedule. As the XBB.1.5 variant emerged during the study, we tested vaccine-induced T cell responses in 10 additional participants using recombinant XBB.1.5 Spike protein. Using an optimized activation-induced marker assay, we quantified circulating Spike-specific CD4+ and CD8+ T cells based on antigen-stimulated expression of CD134, CD69, CD25, CD137, and/or CD107a. Results. Vaccination strongly induced SARS-CoV-2-specific T cells, including BA.4/5- and XBB.1.5-reactive T cells, which remained detectable over time and further increased following a fourth dose. However, responses to BA.4/5 (1.34- to 1.67-fold lower) XBB.1.5 (2.0- to 18-fold lower) were significantly reduced in magnitude compared with ancestral strain responses. CD4+ responses correlated with anti-receptor-binding domain antibodies and predicted subsequent antibody responses in seronegative individuals. Lung transplant recipients receiving prednisone and older adults displayed weaker responses. Conclusions. Ancestral strain vaccination stimulates BA.4/5 and XBB.1.5-cross-reactive T cells in SOTRs, but at lower magnitudes. Antigen-specific T cells can predict future antibody responses. Our data support monitoring both humoral and cellular immunity in SOTRs to track COVID-19 vaccine immunogenicity against emerging variants.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Variants Omicron BA.4/5 and XBB.1.5 Significantly Escape T Cell Recognition in Solid-organ Transplant Recipients Vaccinated Against the Ancestral Strain

Halvorson,

Ivison,

Huang

et al. 2023

Transplantation

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“…As SARS-CoV-2 variants continue to evolve, understanding vaccine immunogenicity in vulnerable populations is critical to informing vaccination strategies. SOTRs show impaired humoral and cellular responses to mRNA vaccines 5,9,28,30 , corresponding with increased susceptibility to infection 4,25 . In the present study, we have provided the first AIM basedcharacterization of COVID-19 vaccine-induced T cell responses in SOTRs.…”

Section: Discussionmentioning

confidence: 99%

“…Vaccination also induces comparatively weaker Spike-specific IFN-γ+ and/or IL-2+ T cell responses than natural infection in SOTRs 29,30 .…”

Section: Covid-19 Vaccines Effectively Reduce Infections Hospitalizat...mentioning

confidence: 98%

SARS-CoV-2 variants Omicron BA.4/5 and XBB.1.5 significantly escape T cell recognition in solid organ transplant recipients vaccinated against the ancestral strain

Halvorson,

Ivison,

Huang

et al. 2023

Preprint

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Background: Immune-suppressed solid organ transplant recipients (SOTRs) display impaired humoral responses to COVID-19 vaccination, but T cell responses are incompletely understood. The highly infectious SARS-CoV-2 variants Omicron BA.4/5 and XBB.1.5 escape neutralization by antibodies induced by vaccination or infection with earlier strains, but T cell recognition of these lineages in SOTRs is unclear. Methods: We characterized Spike-specific T cell responses to ancestral SARS-CoV-2, Omicron BA.4/5 and XBB.1.5 peptides in a prospective study of kidney, lung and liver transplant recipients (n = 42) throughout a three- or four-dose ancestral Spike mRNA vaccination schedule. Using an optimized activation-induced marker assay, we quantified circulating Spike-specific CD4+ and CD8+ T cells based on antigen-stimulated expression of CD134, CD69, CD25, CD137 and/or CD107a. Results: Vaccination strongly induced SARS-CoV-2-specific T cells, including BA.4/5- and XBB.1.5-reactive T cells, which remained detectable over time and further increased following a fourth dose. However, responses to Omicron BA.4/5 and XBB.1.5 were significantly lower in magnitude compared to ancestral strain responses. Antigen-specific CD4+ T cell frequencies correlated with anti-receptor-binding domain (RBD) antibody titres, with post-second dose T cell responses predicting subsequent antibody responses. Patients receiving prednisone, lung transplant recipients and older adults displayed weaker responses. Conclusions: Ancestral strain vaccination stimulates BA.4/5 and XBB.1.5-cross-reactive T cells in SOTRs, but responses to these variants are diminished. Antigen-specific T cells can predict future antibody responses and identify vaccine responses in seronegative individuals. Our data support monitoring both humoral and cellular immunity in SOTRs to track effectiveness of COVID-19 vaccines against emerging variants.

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“…Studies presenting results from flow cytometric analysis demonstrated pooled response rates of 16.1% (95%CI 8.5-25.4%) after the first dose, 73.7% (95%CI 55.2-88.8%; I 2 85.6%) after the second dose, and 86.5% (95%CI 75.3-94.9%; I 2 70.1%) after a third booster dose (Figure 2C). Only six studies included recipients with previous SARS-CoV-2 infection (27,29,30,37,41,45). Supplementary Figure S1 illustrates the cellular immune response rate after excluding the results from these studies, and the results were not different from the primary analyses that included recipients with previous SARS-CoV-2 infection.…”

Section: Cellular Immune Response After Sars-cov-2 Vaccination In Kid...mentioning

confidence: 99%

Cellular immune response of SARS-CoV-2 vaccination in kidney transplant recipients: a systematic review and meta-analysis

Udomkarnjananun¹,

Gatechompol²,

Leelahavanichkul³

et al. 2023

Front. Immunol.

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BackgroundEvidence has demonstrated inferior humoral immune responses after SARS-CoV-2 vaccination in kidney transplant recipients compared to the general population. However, data on cellular immune responses in this population have not been established.MethodsWe searched the MEDLINE, Scopus, and Cochrane databases and included studies reporting cellular immune response rates in kidney transplant recipients after receiving SARS-CoV-2 vaccines. Studies that reported factors associated with cellular immune responders or non-responders were also included (PROSPERO: CRD42022375544).ResultsFrom a total of 1,494 articles searched, 53 articles were included in the meta-analysis. In all, 21 studies assessed cellular immune response by interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISPOT), 22 studies used interferon-γ release assay (IGRA), and 10 studies used flow cytometric analysis. The pooled response rate after two doses (standard regimen) and three doses of vaccination was 47.5% (95%CI 38.4-56.7%) and 69.1% (95%CI 56.3-80.6%) from IFN-γ ELISPOT, 25.8% (95%CI 19.7-32.4%) and 14.7% (95%CI 8.5-22.2%) from IGRA, and 73.7% (95%CI 55.2-88.8%) and 86.5% (95%CI 75.3-94.9%) from flow cytometry, respectively. Recipients with seroconversion were associated with a higher chance of having cellular immune response (OR 2.58; 95%CI 1.89-3.54). Cellular immune response in kidney transplant recipients was lower than in dialysis patients (OR 0.24; 95%CI 0.16-0.34) and the general population (OR 0.10; 95%CI 0.07-0.14). Age and immunosuppressants containing tacrolimus or corticosteroid were associated with inferior cellular immune response.ConclusionCellular immune response after SARS-CoV-2 vaccination in kidney transplant recipients was lower than in dialysis patients and the general population. Age, tacrolimus, and corticosteroid were associated with poor response. Cellular immune response should also be prioritized in vaccination studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022375544.

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Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection

Cited by 9 publications

References 76 publications

SARS-CoV-2 Variants Omicron BA.4/5 and XBB.1.5 Significantly Escape T Cell Recognition in Solid-organ Transplant Recipients Vaccinated Against the Ancestral Strain

SARS-CoV-2 Variants Omicron BA.4/5 and XBB.1.5 Significantly Escape T Cell Recognition in Solid-organ Transplant Recipients Vaccinated Against the Ancestral Strain

SARS-CoV-2 variants Omicron BA.4/5 and XBB.1.5 significantly escape T cell recognition in solid organ transplant recipients vaccinated against the ancestral strain

Cellular immune response of SARS-CoV-2 vaccination in kidney transplant recipients: a systematic review and meta-analysis

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