scholarly journals SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study

2021 ◽  
Author(s):  
Adrian M Shields ◽  
Srinivasan Venkatachalam ◽  
Salim Shafeek ◽  
Shankara Paneesha ◽  
Mark Ford ◽  
...  
Keyword(s):  
B Cell ◽  
Booster Vaccination ◽  
Primary Vaccination ◽  
Oncology Patients ◽  
Vaccine Responses ◽  
Oncological Patients ◽  
B Cell Malignancy ◽  
Rheumatological Disease ◽  
Research Consortium ◽  
The Relationship

Abstract B cell depleting agents are amongst the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B cell depleting agents: a cohort of patients treated for haematological B cell malignancy and another treated for rheumatological disease. B cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B cell reconstitution, however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses, however shorter intervals between vaccine doses (<1m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B cell depleting agents (>36m previously) vaccine non-responsiveness was independent of peripheral B cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2.

scholarly journals Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients

2022 ◽  
Author(s):  
Lu M Yang ◽  
Cristina Costales ◽  
Muthukumar Ramanathan ◽  
Philip L. Bulterys ◽  
Kanagavel Murugesan ◽  
...  
Keyword(s):  
B Cell ◽  
Cellular Response ◽  
Booster Dose ◽  
Booster Vaccination ◽  
Humoral Response ◽  
Primary Vaccination ◽  
Vaccine Response ◽  
Immunosuppressed Patients ◽  
S1p Receptor ◽  
Receptor Modulators

Importance: Data on the humoral and cellular immune response to primary and booster SARS-CoV-2 vaccination in immunosuppressed patients is limited. Objective: To determine humoral and cellular response to primary and booster vaccination in immunosuppressed patients and identify variables associated with poor response. Design: Retrospective observational cohort study. Setting: Large healthcare system in Northern California. Participants: This study included patients fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) who underwent clinical testing for anti-SARS-SoV-2 S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon gamma release assay (IGRA) from January 1, 2021 through November 15, 2021. A cohort of 18 immunocompetent volunteer healthcare workers were included as reference. No participants had a prior diagnosis of SARS-CoV-2 infection. Exposure(s): Immunosuppressive diseases and therapies. Main Outcome(s) and Measure(s): Humoral and cellular SARS-CoV-2 vaccine response as measured by anti-S1 IgG and SARS-CoV-2 IGRA, respectively, after primary and booster vaccination. Results: 496 patients (54% female; median age 50 years) were included in this study. Among immunosuppressed patients after primary vaccination, 62% (261/419) had positive anti-S1 IgG and 71% (277/389) had positive IGRA. After booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Immunosuppressive factors associated with low rates of humoral response after primary vaccination included anti-CD20 monoclonal antibodies (n=48, P<.001), sphingosine 1-phsophate (S1P) receptor modulators (n=11, P<.001), mycophenolate (n=78, P=.002), and B cell lymphoma (n=55, P=.004); those associated with low rates of cellular response included S1P receptor modulators (n=11, P<.001) and mycophenolate (n=69, P<.001). Of patients who responded poorly to primary vaccination, 16% (4/25) with hematologic malignancy or primary immunodeficiency developed a significantly increased humoral response after the booster dose, while 52% (14/27) with solid malignancy, solid organ transplantation, or autoimmune disease developed an increased response (P=.009). Only 5% (2/42) of immunosuppressed patients developed a significantly increased cellular response following the booster dose. Conclusions and Relevance: Cellular vaccine response rates were higher than humoral response rates in immunosuppressed individuals after primary vaccination, particularly among those undergoing B cell targeting therapies. However, humoral response can be increased with booster vaccination, even in patients on B cell targeting therapies.

Reduction of Milk Contamination with Aflatoxin-M1 through Vaccination of Dairy Cattle with Aflatoxin-B1 Vaccine

2020 ◽  
Keyword(s):  
Dairy Cattle ◽  
Aflatoxin B1 ◽  
Booster Vaccination ◽  
Primary Vaccination ◽  
Nano Particles ◽  
Aflatoxin M1 ◽  
Serum Samples ◽  
Serum Albumins ◽  
Milk Contamination ◽  
Before And After

Aflatoxin M1 is one of mycotoxin derivatives, which is secreted in milk of dairy cattle fed on feed contaminated with Aflatoxin-B1 (AFB1). The current study was designed to prepare a vaccine against AFB1and to evaluate its efficacy in reducing or preventing secretion of AFM1 in milk. Aflatoxin-B1 was prepared, purified and transformed into oxime, then it was fixed on bovine serum albumins. The AFB1-BSA conjugate was adjuvanted with Gold Nano particles then Montanide ISA 206. The prepared vaccine was used for immunization of rabbits by S/c routes as 100 µg/dose and dairy cattle by I/M routes as 500 µg/dose. The vaccinated animals were boosted at 3 weeks post primary immunization. Serum samples were collected and examined for the anti-AFB1 using AGPT. A mean titer of 15.2 AGPU/ml was detected at 2 weeks post primary vaccination then significantly increased till reached to 76.8 AGPU/ml at 6 weeks post Booster vaccination. All vaccinated rabbits were challenged with dose of 0.3 mg AFB1 toxin/Kg. The vaccinated rabbit showed 100% protection and no AFB1 toxin residue was detected in their livers. Milk samples were collected from non-vaccinated and AFB1-immunized dairy cattle then examined with ELISA for quantitation of AFM1 residues before and after vaccination. The results showed that the prepared AFB1 vaccine was safe, potent and able to reduce AFM1 release in milk of vaccinated heifers by 70%. So the vaccination of lactating animals with the AFB1vaccine might represent a valid tool for the prevention of AFM1 contamination of milk and dairy products.

scholarly journals Therapeutic Targets in Chronic Lymphocytic Leukemia

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3259
Author(s):  
Luca Laurenti ◽  
Dimitar G. Efremov
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Therapeutic Targets ◽  
Common Type ◽  
Lymphocytic Leukemia ◽  
Western Countries ◽  
B Cell Malignancy ◽  
Adult Leukemia ◽  
Cell Malignancy

Chronic lymphocytic leukemia (CLL) is a common B cell malignancy and is the most common type of adult leukemia in western countries [...]

A broad and systematic approach to identify B-cell malignancy targeting TCRs for multi-antigen based T-cell therapy

2021 ◽  
Author(s):  
Miranda H. Meeuwsen ◽  
Anne K. Wouters ◽  
Lorenz Jahn ◽  
Renate S. Hagedoorn ◽  
Michel G.D. Kester ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Systematic Approach ◽  
T Cell Therapy ◽  
B Cell Malignancy ◽  
Cell Malignancy

EXPRESSION OF IgD ON B CELL MALIGNANCY|An Immunopathological Study of 50 Cases

2008 ◽  
Vol 36 (10) ◽  
pp. 1429-1440
Author(s):  
Shigeo Mori ◽  
Shizuo Hagiwara ◽  
Hideki Kodo ◽  
Noboru Mohri
Keyword(s):  
B Cell ◽  
B Cell Malignancy ◽  
Cell Malignancy

Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-cell malignancy

Cytotherapy ◽  
2003 ◽  
Vol 5 (2) ◽  
pp. 131-138 ◽  
Author(s):  
M.C. Jensen ◽  
L.J.N. Cooper ◽  
A.M. Wu ◽  
S.J. Forman ◽  
A. Raubitschek
Keyword(s):  
T Lymphocytes ◽  
B Cell ◽  
Cytotoxic T Lymphocytes ◽  
B Cell Malignancy ◽  
Cell Malignancy

scholarly journals Selection of a Nuclease-Resistant RNA Aptamer Targeting CD19

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5220
Author(s):  
Carla L. Esposito ◽  
Katrien Van Roosbroeck ◽  
Gianluca Santamaria ◽  
Deborah Rotoli ◽  
Annamaria Sandomenico ◽  
...  
Keyword(s):  
B Cell ◽  
Binding Activity ◽  
Rna Aptamer ◽  
Transmembrane Glycoprotein ◽  
B Cell Malignancy ◽  
A Cell ◽  
Enrichment Protocol ◽  
Interesting Class ◽  
Exponential Enrichment ◽  
Cluster Of Differentiation

The transmembrane glycoprotein cluster of differentiation 19 (CD19) is a B cell–specific surface marker, expressed on the majority of neoplastic B cells, and has recently emerged as a very attractive biomarker and therapeutic target for B-cell malignancies. The development of safe and effective ligands for CD19 has become an important need for the development of targeted conventional and immunotherapies. In this regard, aptamers represent a very interesting class of molecules. Additionally referred to as ‘chemical antibodies’, they show many advantages as therapeutics, including low toxicity and immunogenicity. Here, we isolated a nuclease-resistant RNA aptamer binding to the human CD19 glycoprotein. In order to develop an aptamer also useful as a carrier for secondary reagents, we adopted a cell-based SELEX (Systematic Evolution of Ligands by EXponential Enrichment) protocol adapted to isolate aptamers able to internalise upon binding to their cell surface target. We describe a 2′-fluoro pyrimidine modified aptamer, named B85.T2, which specifically binds to CD19 and shows an exquisite stability in human serum. The aptamer showed an estimated dissociation constant (KD) of 49.9 ± 13 nM on purified human recombinant CD19 (rhCD19) glycoprotein, a good binding activity on human B-cell chronic lymphocytic leukaemia cells expressing CD19, and also an effective and rapid cell internalisation, thus representing a promising molecule for CD19 targeting, as well as for the development of new B-cell malignancy-targeted therapies.

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