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  1. Article ; Online: Cellular and Humoral Immunity after the Third Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplant Recipients

    Laura Thümmler / Michael Koldehoff / Neslinur Fisenkci / Leonie Brochhagen / Peter A. Horn / Adalbert Krawczyk / Monika Lindemann

    Vaccines, Vol 10, Iss 972, p

    2022  Volume 972

    Abstract: Protecting vulnerable groups from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is mandatory. Immune responses after a third vaccination against SARS-CoV-2 are insufficiently studied in patients after hematopoietic stem-cell ...

    Abstract Protecting vulnerable groups from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is mandatory. Immune responses after a third vaccination against SARS-CoV-2 are insufficiently studied in patients after hematopoietic stem-cell transplantation (HSCT). We analyzed immune responses before and after a third vaccination in HSCT patients and healthy controls. Cellular immunity was assessed using interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpots. Furthermore, this is the first report on neutralizing antibodies against 11 variants of SARS-CoV-2, analyzed by competitive fluorescence assay. Humoral immunity was also measured by neutralization tests assessing cytopathic effects and by ELISA. Neither HSCT patients nor healthy controls displayed significantly higher SARS-CoV-2-specific IFN-γ or IL-2 responses after the third vaccination. However, after the third vaccination, cellular responses were 2.6-fold higher for IFN-γ and 3.2-fold higher for IL-2 in healthy subjects compared with HSCT patients. After the third vaccination, neutralizing antibodies were significantly higher ( p < 0.01) in healthy controls, but not in HSCT patients. Healthy controls vs. HSCT patients had 1.5-fold higher concentrations of neutralizing antibodies against variants and 1.2-fold higher antibody concentrations against wildtype. However, half of the HSCT patients exhibited neutralizing antibodies to variants of SARS-CoV-2, which increased only slightly after a third vaccination.
    Keywords ELISpot ; variants of concern ; vaccination response ; T cells ; Medicine ; R
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Comparison of SARS-CoV-2- and HCoV-Specific T Cell Response Using IFN-γ ELISpot

    Laura Thümmler / Sina Schwarzkopf / Dietmar Knop / J. Alexander Ross / Victoria Berg / Peter A. Horn / Monika Lindemann

    Diagnostics, Vol 11, Iss 1439, p

    2021  Volume 1439

    Abstract: Herd immunity is essential to control severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), especially in immunocompromised patients. Convalescent individuals should be vaccinated later due to vaccine shortage, as studies show that ... ...

    Abstract Herd immunity is essential to control severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), especially in immunocompromised patients. Convalescent individuals should be vaccinated later due to vaccine shortage, as studies show that neutralizing antibodies generated during infection are stable for at least 6 months. Cellular immunity is also detectable for months. However, there is evidence of cross-reactivity of T cells with human endemic coronaviruses (HCoVs). Here, we show that cross-reactivity—which may prevent the specific detection of SARS-CoV-2-specific T cell responses—can be avoided if cells are stimulated with the N-terminus of the spike protein in IFN-γ ELISpot. In contrast to previous studies, we examined T-cell responses against all four known HCoVs using IFN-γ ELISpot in 19 convalescent volunteers and 10 fully vaccinated volunteers. In addition, we performed Spearman analyses to detect cross-reactivity of T cells. We observed no correlation between T-cell responses against SARS-CoV-2 and human endemic coronaviruses, either in the whole cohort or in the individual groups. The use of the respective stimuli could lead to a more accurate assessment of cellular immunity in recovered individuals. This testing procedure could help to define the best time point at which convalescents should receive SARS-CoV-2 vaccination.
    Keywords cross-reactivity ; ELISpot ; human endemic coronavirus ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Cellular and Humoral Immunity against Different SARS-CoV-2 Variants Is Detectable but Reduced in Vaccinated Kidney Transplant Patients

    Laura Thümmler / Anja Gäckler / Maren Bormann / Sandra Ciesek / Marek Widera / Hana Rohn / Neslinur Fisenkci / Mona Otte / Mira Alt / Ulf Dittmer / Peter A. Horn / Oliver Witzke / Adalbert Krawczyk / Monika Lindemann

    Vaccines, Vol 10, Iss 8, p

    2022  Volume 1348

    Abstract: In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. ... ...

    Abstract In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. Cellular responses were analyzed by interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpot assays. Neutralizing antibody titers were assessed against SARS-CoV-2 D614G (wild type) and the variants alpha, delta, and omicron by a cell culture-based neutralization assay. Humoral immunity was also determined by a competitive fluorescence assay, using 11 different variants of SARS-CoV-2. Antibody ratios were measured by ELISA. KTX patients showed significantly lower SARS-CoV-2-specific IFN-γ responses after booster vaccination than healthy controls. However, SARS-CoV-2-specific IL-2 responses were comparable to the T cell responses of healthy controls. Cell culture-based neutralizing antibody titers were 1.3-fold higher in healthy controls for D614G, alpha, and delta, and 7.8-fold higher for omicron ( p < 0.01). Healthy controls had approximately 2-fold higher concentrations of potential neutralizing antibodies against all 11 variants than KTX patients. However, more than 60% of the KTX patients displayed antibodies to variants of SARS-CoV-2. Thus, KTX patients should be partly protected, due to neutralizing antibodies to variants of SARS-CoV-2 or by cross-reactive T cells, especially those producing IL-2.
    Keywords ELISpot ; T cells ; vaccination ; Medicine ; R
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Cellular Immunity in COVID-19 Convalescents with PCR-Confirmed Infection but with Undetectable SARS-CoV-2–Specific IgG

    Sina Schwarzkopf / Adalbert Krawczyk / Dietmar Knop / Hannes Klump / Andreas Heinold / Falko M. Heinemann / Laura Thümmler / Christian Temme / Marianne Breyer / Oliver Witzke / Ulf Dittmer / Veronika Lenz / Peter A. Horn / Monika Lindemann

    Emerging Infectious Diseases, Vol 27, Iss 1, Pp 122-

    2021  Volume 129

    Abstract: We investigated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a group of convalescent, potential blood donors in Germany who had PCR-confirmed SARS-CoV-2 infection. Sixty days after onset of symptoms, 13/78 ( ... ...

    Abstract We investigated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a group of convalescent, potential blood donors in Germany who had PCR-confirmed SARS-CoV-2 infection. Sixty days after onset of symptoms, 13/78 (17%) study participants had borderline or negative results to an ELISA detecting IgG against the S1 protein of SARS-CoV-2. We analyzed participants with PCR-confirmed infection who had strong antibody responses (ratio >3) as positive controls and participants without symptoms of SARS-CoV-2 infection and without household contact with infected patients as negative controls. Using interferon-γ ELISpot, we observed that 78% of PCR-positive volunteers with undetectable antibodies showed T cell immunity against SARS-CoV-2. We observed a similar frequency (80%) of T-cell immunity in convalescent donors with strong antibody responses but did not detect immunity in negative controls. We concluded that, in convalescent patients with undetectable SARS-CoV-2 IgG, immunity may be mediated through T cells.
    Keywords coronavirus disease ; SARS-CoV-2 ; severe acute respiratory syndrome coronavirus 2 ; severe acute respiratory syndrome ; SARS ; viruses ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Humoral and Cellular Vaccination Responses against SARS-CoV-2 in Hematopoietic Stem Cell Transplant Recipients

    Monika Lindemann / Vesna Klisanin / Laura Thümmler / Neslinur Fisenkci / Nikolaos Tsachakis-Mück / Markus Ditschkowski / Sina Schwarzkopf / Hannes Klump / Hans Christian Reinhardt / Peter A. Horn / Michael Koldehoff

    Vaccines, Vol 9, Iss 1075, p

    2021  Volume 1075

    Abstract: The cellular response to SARS-CoV-2 vaccination and infection in allogeneic hematopoietic stem cell transplant (HSCT) recipients is not yet clear. In the current study, HSCT recipients prior to and post vaccination were tested for SARS-CoV-2-specific ... ...

    Abstract The cellular response to SARS-CoV-2 vaccination and infection in allogeneic hematopoietic stem cell transplant (HSCT) recipients is not yet clear. In the current study, HSCT recipients prior to and post vaccination were tested for SARS-CoV-2-specific humoral and cellular immunity. Antibodies against spike (S) 1 were assessed by Anti-SARS-CoV-2 IgG ELISA (Euroimmun). Cellular immunity was analyzed by an in house interferon-gamma ELISpot and T-SPOT. COVID (Oxford Immunotec), using altogether seven SARS-CoV-2-specific antigens. In 117 HSCT patients vaccinated twice, SARS-CoV-2 IgG antibodies were significantly higher than in HSCT controls pre vaccination ( p < 0.0001). After the second vaccination, we observed a median antibody ratio of 4.7 and 68% positive results, whereas 35 healthy controls reached a median ratio of 9.0 and 100% positivity. ELISpot responses in patients were significantly ( p < 0.001) reduced to ≤33% of the controls. After the second vaccination, female HSCT patients and female healthy controls showed significantly higher antibody responses than males (6.0 vs. 2.1 and 9.2 vs. 8.2, respectively; p < 0.05). Cellular immunity was diminished in patients irrespective of sex. In conclusion, especially male HSCT recipients showed impaired antibody responses after SARS-CoV-2 vaccination. Changing the vaccine schedule or composition could help increase vaccine responses.
    Keywords SARS-CoV-2 ; vaccination ; allogeneic hematopoietic stem cell transplantation ; antibodies ; ELISpot ; sex-dependency ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Long-Term SARS-CoV-2 Specific Immunity Is Affected by the Severity of Initial COVID-19 and Patient Age

    Margarethe Konik / Monika Lindemann / Markus Zettler / Lara Meller / Sebastian Dolff / Vera Rebmann / Peter A. Horn / Ulf Dittmer / Adalbert Krawczyk / Leonie Schipper / Mirko Trilling / Olympia Evdoxia Anastasiou / Sina Schwarzkopf / Laura Thümmler / Christian Taube / Christoph Schöbel / Thorsten Brenner / Eva-Maria Skoda / Benjamin Wilde /
    Anja Gäckler / Oliver Witzke / Hana Rohn

    Journal of Clinical Medicine, Vol 10, Iss 4606, p

    2021  Volume 4606

    Abstract: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the ... ...

    Abstract The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients’ humoral immune responses to Spike (S) protein over the long-term, whereas the patients’ age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity.
    Keywords COVID-19 ; SARS-CoV-2 ; immunity ; age ; T cell ; SARS-CoV-2 IgG ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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