scholarly journals Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression

2021 ◽  
pp. annrheumdis-2021-220626
Author(s):  
Maria Prendecki ◽  
Candice Clarke ◽  
Helena Edwards ◽  
Stacey McIntyre ◽  
Paige Mortimer ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Glomerular Diseases ◽  
Cell Responses ◽  
The Impact ◽  
Dose Vaccine

ObjectiveThere is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination.MethodsSerological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases.ResultsFollowing first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.

scholarly journals B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asuka Tanaka ◽  
Kentaro Ide ◽  
Yuka Tanaka ◽  
Masahiro Ohira ◽  
Hiroyuki Tahara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Anti Cd20

AbstractPretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients’ immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4+ T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4+ T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4+ T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4+ T cell response. The depletion of the CD5+ B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10+ CD5+ B cells suppress the excessive response of anti-donor CD4+ T cells responses in sensitized recipients.

scholarly journals B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation

2015 ◽  
Vol 16 (2) ◽  
pp. 672-678 ◽  
Author(s):  
J. Marino ◽  
J. T. Paster ◽  
A. Trowell ◽  
L. Maxwell ◽  
K. H. Briggs ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Memory T Cell ◽  
Cell Responses ◽  
Cd20 Antibody ◽  
Anti Cd20

scholarly journals B-CELL DEPLETION WITH ANTI-CD20 MAB EXACERBATES ANTI-DONOR CD4 POSITIVE T-CELL RESPONSES IN HIGHLY SENSITIZED TRANSPLANT MODEL

2020 ◽  
Vol 104 (S3) ◽  
pp. S121-S121
Author(s):  
Asuka Tanaka ◽  
Kentaro Ide ◽  
Yuka Tanaka ◽  
Masahiro Ohira ◽  
Hiroyuki Tahara ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Responses ◽  
Anti Cd20 ◽  
Transplant Model

scholarly journals SARS-CoV-2 Spike-Specific T-Cell Responses in Patients With B-Cell Depletion Who Received Chimeric Antigen Receptor T-Cell Treatments

JAMA Oncology ◽  
2021 ◽  
Author(s):  
Kalpana Parvathaneni ◽  
Kyabeth Torres-Rodriguez ◽  
Wenzhao Meng ◽  
Wei-Ting Hwang ◽  
Noelle Frey ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Responses

scholarly journals Contrasting effects of B cell depletion on CD4 + and CD8 + memory T cell responses generated after transplantation

2020 ◽  
Vol 20 (9) ◽  
pp. 2551-2558
Author(s):  
Jose Marino ◽  
Bruno Gonzalez‐Nolasco ◽  
Xianding Wang ◽  
William Orent ◽  
Gilles Benichou
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Memory T Cell ◽  
Cell Responses

B Cell Depletion of Naïve Recipients Enhances Graft Reactive T Cell Responses.

2014 ◽  
Vol 98 ◽  
pp. 20
Author(s):  
T. Singh ◽  
K. Jiang ◽  
R. Ippolito ◽  
B. Ramaswami ◽  
F. Lund ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Responses

Id/KLH Vaccine (FavId™) Following Treatment with Rituximab: An Analysis of Response Rate Improvement (RRI) and Time-to-Progression (TTP) in Follicular Lymphoma (FL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 587-587 ◽  
Author(s):  
Omer N. Koc ◽  
Charles Redfern ◽  
Peter H. Wiernik ◽  
Fred Rosenfelt ◽  
Jane N. Winter ◽  
...  
Keyword(s):  
T Cell ◽  
Injection Site ◽  
B Cell ◽  
Single Agent ◽  
Injection Site Reaction ◽  
T Cell Response ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Gm Csf

Abstract Background: Id/KLH vaccine (FavId) administered as a single agent has been associated with tumor regressions in patients with relapsed/refractory (RR) FL. B-cell depletion has been demonstrated to augment the T-cell immune response to subsequent vaccine administration in mice (Qin 1998 Nat Med 4:627). Objective: To evaluate the efficacy and safety of Id-KLH administered during the period of rituximab induced B-cell depletion. Eligibility: FL pts who were: treatment naïve (TN); RR following chemotherapy; or relapsed following rituximab. Treatment: Following rituximab (375mg/m2 i.v. weekly x 4) pts received Id-KLH (1 mg s.q. monthly x 6) starting on week 12. GM-CSF, 250 mcg, was administered s.q. at the Id-KLH injection site on days 1–4. Pts could continue Id-KLH until progression. Results: 103 pts received rituximab. Response to rituximab at month 3 was 35% (3-CR; 33-PR). Eleven (11) pts were PD following rituximab (11%). Id/KLH could not be made for 4 pts (4%). Eighty-eight (88) pts were begun on Id-KLH. Among the 45 RR pts, 32 (72%) have not progressed at a median follow-up of 12 months compared with 40% of historical control pts treated with rituximab alone (Witzig 2002 JCO 20:2453). Among the 43 TN pts, 82% have not progressed after a median follow-up of 9 months. RRI (SD to PR, PR to CR after month 3) was observed in 21 pts (12-SD to PR; 9-PR to CR). Robust T-cell responses to both Id and KLH were observed (3 of 3 pts tested). Anti-KLH antibody responses were generally not seen until B-cell recovery. The most frequent adverse event was an injection site reaction. A flu-like syndrome was also observed consistent with GM-CSF administration. Conclusion: Id/KLH vaccine (FavId), administered to pts with FL during a period of B-cell depletion induced by rituximab, can result in an anti-Id T-cell response, and appears to result in an RRI and an increased TTP compared to historical controls. A randomized, double-blind, placebo-controlled, Phase 3 trial of rituximab + FavId has been initiated.

Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

2019 ◽  
Vol 71 (4) ◽  
pp. 641-650 ◽  
Author(s):  
Antoine Néel ◽  
Marie Bucchia ◽  
Mélanie Néel ◽  
Gaelle Tilly ◽  
Aurélie Caristan ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Response ◽  
Cd8 T Cell ◽  
Antineutrophil Cytoplasmic Antibody ◽  
T Cell Response ◽  
Cell Depletion ◽  
B Cell Depletion

scholarly journals Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

2021 ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
T Cell Response ◽  
Potential Threat ◽  
Cell Responses ◽  
Reference Isolate ◽  
The Impact

Abstract Both natural infection with SARS-CoV-2 and immunization with vaccines induce protective immunity. However, the extent to which such immune responses protect against emerging variants is of increasing importance. Such variants of concern (VOC) include isolates of lineage B.1.1.7, first identified in the UK, and B.1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417, escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks of the receptor-binding domain. To address the potential threat posed by VOC, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort sampled in the early convalescent stages after natural infection in the first wave of the pandemic in Spring 2020. We tested antibody and T cell responses against a reference isolate of the original circulating lineage, B, and the impact of sequence variation in the B.1.1.7 and B.1.351 VOC. Neutralization of the VOC compared to B isolate was reduced, and this was most evident for the B.1.351 isolate. This reduction in antibody neutralization was less marked in post-boost vaccine-induced responses compared to naturally induced immune responses and could be largely explained by the potency of the homotypic antibody response. After a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOC was completely abrogated in the majority of vaccinees. Importantly, high magnitude T cell responses were generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. These data indicate that VOC may evade protective neutralizing responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine dose, but the impact of the VOC on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants.

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