scholarly journals Deep dissection of the antiviral immune profile of patients with COVID-19

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Djordje Atanackovic ◽  
Stephanie V. Avila ◽  
Forat Lutfi ◽  
Diego de Miguel-Perez ◽  
Xiaoxuan Fan ◽  
...  

AbstractIn light of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants potentially undermining humoral immunity, it is important to understand the fine specificity of the antiviral antibodies. We screened 20 COVID-19 patients for antibodies against 9 different SARS-CoV-2 proteins observing responses against the spike (S) proteins, the receptor-binding domain (RBD), and the nucleocapsid (N) protein which were of the IgG1 and IgG3 subtypes. Importantly, mutations which typically occur in the B.1.351 “South African” variant, significantly reduced the binding of anti-RBD antibodies. Nine of 20 patients were critically ill and were considered high-risk (HR). These patients showed significantly higher levels of transforming growth factor beta (TGF-β) and myeloid-derived suppressor cells (MDSC), and lower levels of CD4+ T cells expressing LAG-3 compared to standard-risk (SR) patients. HR patients evidenced significantly higher anti-S1/RBD IgG antibody levels and an increased neutralizing activity. Importantly, a large proportion of S protein-specific antibodies were glycosylation-dependent and we identified a number of immunodominant linear epitopes within the S1 and N proteins. Findings derived from this study will not only help us to identify the most relevant component of the anti-SARS-CoV-2 humoral immune response but will also enable us to design more meaningful immunomonitoring methods for anti-COVID-19 vaccines.

Microbiology ◽  
2005 ◽  
Vol 151 (6) ◽  
pp. 2065-2074 ◽  
Author(s):  
Yukiko Fujita ◽  
Takeshi Doi ◽  
Koji Sato ◽  
Ikuya Yano

Humoral immune responses of active TB patients against six mycobacterial lipid antigens [trehalose 6,6′-dimycolate (TDM) from Mycobacterium bovis BCG (TDM-T) and Mycobacterium avium complex (TDM-M), trehalose 6-monomycolate (TMM) from M. bovis BCG (TMM-T) and M. avium complex (TMM-M), triacyl (PL-2) and tetraacyl (PL-1) phosphatidylinositol dimannosides] were examined by ELISA. IgG antibodies of TB patients with active disease reacted against the six lipid antigens distinctively, but heterogeneously. If tests were combined and an overall positive was scored cumulatively when any one of the six tests was positive, a good discrimination between patient and normal subject was obtained. A positive result in any one of the six tests was obtained in 91·5 % of all 924 hospitalized patients and 93·3 % of 210 patients at their first visit to the outpatient clinic. The IgG antibody response differed considerably from patient to patient, and the response patterns were grouped into several types. IgG antibody levels paralleled the bacterial burden; however, the smear-negative (culture-positive) patient group also showed high positive rates and mean ELISA ΔA values against the six lipid antigens. There were also marked differences in positive rate and mean ΔA values between cavity-positive and -negative groups, the former being higher than the latter. After anti-TB chemotherapy was initiated, IgG antibody levels decreased dramatically, paralleling the decrease in the amount of excretion of bacteria. Since multiple-antigen ELISA using particular lipid antigens was highly sensitive, and IgG antibody levels vary greatly at different stages of the disease, this technique is applicable for early diagnosis of smear-negative (and -positive) active TB and the prognosis for completion of anti-TB chemotherapy.


Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 171
Author(s):  
Richard Vollenberg ◽  
Phil-Robin Tepasse ◽  
Joachim Ewald Kühn ◽  
Marc Hennies ◽  
Markus Strauss ◽  
...  

Severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. Vaccination is considered the core approach to containing the pandemic. There is currently insufficient evidence on the efficacy of these vaccines in immunosuppressed inflammatory bowel disease (IBD) patients. The aim of this study was to investigate the humoral response in immunosuppressed IBD patients after COVID-19 mRNA vaccination. In this prospective study, IgG antibody levels (AB) against the SARS-CoV-2 receptor-binding domain (spike-protein) were quantitatively determined. For assessing the potential neutralizing capacity, a SARS-CoV-2 surrogate neutralization test (sVNT) was employed in IBD patients (n = 95) and healthy controls (n = 38). Sera were examined prior to the first/second vaccination and 3/6 months after second vaccination. Patients showed lower sVNT (%) and IgG-S (AU/mL) AB both before the second vaccination (sVNT p < 0.001; AB p < 0.001) and 3 (sVNT p = 0.002; AB p = 0.001) and 6 months (sVNT p = 0.062; AB p = 0.061) after the second vaccination. Although seroconversion rates (sVNT, IgG-S) did not differ between the two groups 3 months after second vaccination, a significant difference was seen 6 months after second vaccination (sVNT p = 0.045). Before and three months after the second vaccination, patients treated with anti-tumor necrosis factor (TNF) agents showed significantly lower AB than healthy subjects. In conclusion, an early booster shot vaccination should be discussed for IBD patients on anti-TNF therapy.


2021 ◽  
Author(s):  
Maria Skaalum Petersen ◽  
Cecilie Bo Hansen ◽  
Marnar Fridheim Kristiansen ◽  
Jogvan Pall Fjallsbak ◽  
Solrun Larsen ◽  
...  

Only a few studies have assessed the long-term duration of the humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2). In this nationwide longitudinal study from the Faroe Islands with close to full participation of all individuals on the Islands with PCR confirmed COVID-19 during the two waves of infections in the spring and autumn 2020 (n=172 & n=233), samples were drawn at three longitudinal time points (3, 7 and 12 months and 1, 3 and 7 months after disease onset, respectively). Serum was analyzed with a direct quantitative IgG antibody binding ELISA to detect anti–SARS–CoV–2 spike RBD antibodies and a commercially available qualitative sandwich RBD ELISA kit measuring total antibody binding. The seropositive rate in the convalescent individuals was above 95 % at all sampling time points for both assays. There was an overall decline in IgG titers over time in both waves (p < 0.001). Pairwise comparison showed that IgG declined significantly from the first sample until approximately 7 months in both waves (p < 0.001). After that, the antibody level still declined significantly (p < 0.001), but decelerated with an altered slope remaining fairly stable from 7 months to 12 months after infection. Interestingly, the IgG titers followed a U-shaped curve with higher antibody levels among the oldest (67+) and the youngest (0–17) age groups compared to intermediate groups (p < 0.001). Our results indicate that COVID–19 convalescent individuals are likely to be protected from reinfection up to 12 months after symptom onset and maybe even longer. We believe our results can add to the understanding of natural immunity and the expected durability of SARS–CoV–2 vaccine immune responses.


2017 ◽  
Vol 6 (1) ◽  
pp. 1-14
Author(s):  
Juan F. Santibanez ◽  
Suncica Bjelica

Background: Transforming growth factor-beta1 (TGF-β1) is a pleiotropic cytokine with a double role in cancer through its capacity to inhibit early stages of tumors while enhancing tumor progression at late stages of tumor progression. Moreover, TGF-β1 is a potent immunosuppressive cytokine within the tumor microenvironment that allows cancer cells to escape from immune surveillance, which largely contributes to the tumor progression. Method: It has been established that the cancer progression is commonly associated with increased number of Myeloid-derived suppressor cells (MDSC) that are a hallmark of cancer and a key mechanism of immune evasion. Result: MDSC represent a population of heterogeneous myeloid cells comprised of macrophages, granulocytes and dendritic cells at immature stages of development. MDSC promote tumor progression by regulating immune responses as well as tumor angiogenesis and cancer metastasis. Conclusion: In this review, we present an overview of the main key functions of both TGF-β1 and MDSC in cancer and in the immune system. Furthermore, the mutual contribution between TGF-β1 and MDSC in the regulation of immune system and cancer development will be analyzed.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2614
Author(s):  
Michał Zarobkiewicz ◽  
Wioleta Kowalska ◽  
Sylwia Chocholska ◽  
Waldemar Tomczak ◽  
Agata Szymańska ◽  
...  

In the current study, we analysed the role and prognostic value of myeloid-derived suppressor cells (MDSC) in chronic lymphocytic leukaemia (CLL). The frequency of circulating monocytic MDSC (M-MDSC; defined as CD14+CD11b+CD15-HLA-DR-/low cells) was assessed in correlation with clinical and laboratory parameters characterising the disease activity and patient immune status. Samples of peripheral blood from untreated CLL patients and healthy volunteers were stained with monoclonal antibodies for flow cytometry analysis. CLL patients with M-MDSC percentages above 9.35% (according to the receiver operating characteristic (ROC) analysis) had a shorter time-to-treatment and shorter survival time than the group with a lower percentage of M-MDSC. The M-MDSC percentage was higher in patients with adverse prognostic factors (i.e., 17p and 11q deletion and CD38 and ZAP-70 expression). A high M-MDSC percentage was linked to significantly lower expression of the CD3ζ in T cells. Furthermore, an analysis of immune regulatory molecules (arginase 1 (ARG1), nitric oxide synthase (NOS2), indoleamine 2,3-dioxygenase (IDO), transforming growth factor beta (TGF-β), and interleukin (IL)-10) was performed. By the means of flow cytometry and RT-qPCR, we showed an overexpression of three of them in M-MDSC of CLL patients. M-MDSC cells seem to be an important factor in the immunosuppressive microenvironment of CLL and seem to be a good and novel prognostic factor


2020 ◽  
Author(s):  
Mary K. Young ◽  
Christine Kornmeier ◽  
Rebecca M. Carpenter ◽  
Nick R. Natale ◽  
Jennifer M. Sasson ◽  
...  

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a pandemic of the respiratory disease coronavirus disease 2019 (COVID-19). Antibody testing is essential to identify persons exposed to the virus and potentially in predicting disease immunity. 183 COVID-19 patients (68 of whom required mechanical ventilation) and 41 controls were tested for plasma IgG, IgA and IgM against the SARS-CoV-2 S1, S2, receptor binding domain (RBD) and N proteins using the MILLIPLEX® SARS-CoV-2 Antigen Panel. Plasma cytokines were concurrently measured using the MILLIPLEX® MAP Human Cytokine/Chemokine/Growth Factor Panel A. As expected the 183 COVID-19 positive patients had high levels of IgG, IgA and IgM anti-SARS-CoV-2 antibodies against each of the viral proteins. Sensitivity of anti-S1 IgG increased from 60% to 93% one week after symptom onset. S1-IgG and S1-IgA had specificities of 98% compared to the 41 COVID-19 negative patients. The 68 ventilated COVID-19 positive patients had higher antibody levels than the 115 COVID-19 positive patients who were not ventilated. IgG antibody levels against S1 protein had the strongest positive correlation to days from symptom onset. There were no statistically significant differences in IgG, IgA and IgM antibodies against S1 based on age. We found that patients with the highest levels of anti-SARS-CoV-2 antibodies had the lowest viral load in the nasopharynx. Finally there was a correlation of high plasma IL-10 with low anti-SARS-CoV-2 antibodies. Anti-SARS-CoV-2 antibody levels, as measured by a novel antigen panel, increased within days after symptom onset, achieving > 90% sensitivity and specificity within one week, and were highest in patients who required mechanical ventilation. Antibody levels were inversely associated with viral load but did not differ as a function of age. The correlation of high IL-10 with low antibody response suggests a potentially suppressive role of this cytokine in the humoral immune response in COVID-19.


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