Cellular immunity predominates over humoral immunity after homologous and heterologous mRNA and vector-based COVID-19 vaccine regimens in solid organ transplant recipients

Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2–specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2–specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2–specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2–specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals

Immunogenicity and reactogenicity of a heterologous COVID-19 prime-boost vaccination compared with homologous vaccine regimens

Heterologous priming with the ChAdOx1-nCoV-19 vector-vaccine followed by boosting with an mRNA-vaccine is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. Here we show that the heterologous regimen induced spike-specific IgG, neutralizing antibodies, and spike-specific CD4 T-cells, which were significantly more pronounced than after homologous vector boost, and higher or comparable in magnitude to the homologous mRNA regimens. Moreover, spike-specific CD8 T-cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Cytokine expression profiling showed a predominance of polyfunctional T-cells expressing IFNγ, TNFα and IL-2 with subtle differences between regimens. Both recipients of the homologous vector-regimen and the heterologous vector/mRNA-combination were most affected by the priming vector-vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA-boosting. Taken together, heterologous vector-mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profile. This knowledge will have implications for future vaccine strategies

High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19

BACKGROUND. Patients infected with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2– specific immunity correlate with disease severity. METHODS. In this study, SARS-CoV-2–specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2–specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2–specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls. RESULTS. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2–specific T cells as compared with convalescent individuals. SARS-CoV-2–specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2–specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2–specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general. CONCLUSION. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung. FUNDING. The study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung

High levels of SARS-CoV-2 specific T-cells with restricted functionality in patients with severe course of COVID-19

Patients infected with SARS-CoV-2 differ in the severity of disease. In this study, SARS-CoV-2 specific T-cells and antibodies were characterized in patients with different COVID-19 related disease severity. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2 specific T-cells as compared to convalescent individuals. SARS-CoV-2 specific CD4 T-cells dominated over CD8 T-cells and closely correlated with the number of plasmablasts and SARS-CoV-2 specific IgA- and IgG-levels. Unlike in convalescents, SARS-CoV-2 specific T-cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 and CD8 T-cells in general. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered phenotype may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung

Simple Questionnaires to Improve Pooling Strategies for SARS-CoV-2 Laboratory Testing

Background: Liberal PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to contain the coronavirus disease 2019 (COVID-19) pandemic. Combined multi-sample testing in pools instead of single tests might enhance laboratory capacity and reduce costs, especially in low- and middle-income countries. Objective: The purpose of our study was to assess the value of a simple questionnaire to guide and further improve pooling strategies for SARS-CoV-2 laboratory testing. Methods: Pharyngeal swabs for SARS-CoV-2 testing were obtained from healthcare and police staff, hospital inpatients, and nursing home residents in the southwestern part of Germany. We designed a simple questionnaire, which included questions pertaining to a suggestive clinical symptomatology, recent travel history, and contact with confirmed cases to stratify an individual’s pre-test probability of having contracted COVID-19. The questionnaire was adapted repeatedly in face of the unfolding pandemic in response to the evolving epidemiology and observed clinical symptomatology. Based on the response patterns, samples were either tested individually or in multi-sample pools. We compared the pool positivity rate and the number of total PCR tests required to obtain individual results between this questionnaire-based pooling strategy and randomly assembled pools. Findings: Between March 11 and July 5, 2020, we processed 25,978 samples using random pooling (n = 6,012; 23.1%) or questionnaire-based pooling (n = 19,966; 76.9%). The overall prevalence of SARS-CoV-2 was 0.9% (n = 238). Pool positivity (14.6% vs. 1.2%) and individual SARS-CoV-2 prevalence (3.4% vs. 0.1%) were higher in the random pooling group than in the questionnaire group. The average number of PCR tests needed to obtain the individual result for one participant was 0.27 tests in the random pooling group, as compared to 0.09 in the questionnaire-based pooling group, leading to a laboratory capacity increase of 73% and 91%, respectively, as compared to single PCR testing. Conclusions: Strategies that combine pool testing with a questionnaire-based risk stratification can increase laboratory testing capacities for COVID-19 and might be important tools, particularly in resource-constrained settings

Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties

Background: Several beneficial effects have been demonstrated for secretogranin II (SgII) in non-cardiac tissue. As cardiac production of chromogranin A and B, two related proteins, is increased in heart failure (HF), we hypothesized that SgII could play a role in cardiovascular pathophysiology. Methodology/Principal Findings: SgII production was characterized in a post-myocardial infarction heart failure (HF) mouse model, functional properties explored in experimental models, and circulating levels measured in mice and patients with stable HF of moderate severity. SgII mRNA levels were 10.5 fold upregulated in the left ventricle (LV) of animals with myocardial infarction and HF (p<0.001 vs. sham-operated animals). SgII protein levels were also increased in the LV, but not in other organs investigated. SgII was produced in several cell types in the myocardium and cardiomyocyte synthesis of SgII was potently induced by transforming growth factor-beta and norepinephrine stimulation in vitro. Processing of SgII to shorter peptides was enhanced in the failing myocardium due to increased levels of the proteases PC1/3 and PC2 and circulating SgII levels were increased in mice with HF. Examining a pathophysiological role of SgII in the initial phase of post-infarction HF, the SgII fragment secretoneurin reduced myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by 30% and rapidly increased cardiomyocyte Erk1/2 and Stat3 phosphorylation. SgII levels were also higher in patients with stable, chronic HF compared to age-and gender-matched control subjects: median 0.16 (Q1-3 0.14-0.18) vs. 0.12 (0.10-0.14) nmol/L, p<0.001. Conclusions: We demonstrate increased myocardial SgII production and processing in the LV in animals with myocardial infarction and HF, which could be beneficial as the SgII fragment secretoneurin protects from ischemia-reperfusion injury and cardiomyocyte apoptosis. Circulating SgII levels are also increased in patients with chronic, stable HF and may represent a new cardiac biomarker

Lehrbuch der gesammten Messkunst : oder Darstellung der Theorie und Praxis : zum Selbststudium und Unterricht

bearbeitet von Dr. C.F. Schneitle

Die Instrumente und Werkzeuge der höheren und niederen Messkunst, sowie der geometrischen Zeichnenkunst, ihre Theorie, Construction, Gebrauch und Prüfung

zum Unterricht und Selbststudium bearb. von C. F. Schneitle

Is ipsilateral administration of COVID-19 vaccine boosters the optimal approach?

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