Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Apostolidis, Sokratis A.; Kakara, Mihir; Painter, Mark M.; Goel, Rishi R.; Mathew, Divij; Lenzi, Kerry; Rezk, Ayman; Patterson, Kristina R.; Espinoza, Diego A.; Kadri, Jessy C.; Markowitz, Daniel M.; Markowitz, Clyde; Mexhitaj, Ina; Jacobs, Dina; Babb, Allison; Betts, Michael R.; Prak, Eline T. Luning; Weiskopf, Daniela; Grifoni, Alba; Lundgreen, Kendall A.; Gouma, Sigrid; Sette, Alessandro; Bates, Paul; Hensley, Scott E.; Greenplate, Allison R.; Wherry, E. John; Li, Rui; Bar‐Or, Amit

doi:10.1101/2021.06.23.21259389

Cited by 43 publications

(34 citation statements)

References 87 publications

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“…Plasma IgM, IgG, and IgA responses to SARS-CoV-2 receptor binding domain (RBD) were measured by enzyme linked immunosorbent assay (ELISA) 3 . As reported by others 2,[4][5][6] there was a significant increase in IgG reactivity to RBD between prime and boost (p<0.0001, Fig. 1a).…”

Section: Plasma Binding and Neutralization Assayssupporting

confidence: 85%

Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination

Cho

Muecksch

Schaefer-Babajew

et al. 2021

Preprint

163

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested. Here, we examine memory B cell evolution 5 months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccines in a cohort of SARS-CoV-2 naive individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge 5 months after vaccination of naive individuals express antibodies that are equivalent to those that dominate the initial response. We conclude that memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines would produce a quantitative increase in plasma neutralizing activity but not the qualitative advantage against variants obtained by vaccinating convalescent individuals.

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Section: Plasma Binding and Neutralization Assayssupporting

confidence: 85%

Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination

Cho

Muecksch

Schaefer-Babajew

et al. 2021

Preprint

163

View full text Add to dashboard Cite

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“…In one recent study, 10/13 patients with haematological malignancy and COVID-19 had SsT-cells, which were associated with improved survival (including in those on anti-CD20 therapy). 11 Overall, the emerging data from our study and others 37 appear to suggest that T-cell responses are likely important in those with haematological malignancies and may offer protection from severe COVID-19 in the absence of humoral responses.…”

Section: Sars-cov-2-infected Cancer Patients Were Previously Shown To Have Depleted T-cells Whichsupporting

confidence: 51%

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Fendler¹,

Au²,

Shepherd³

et al. 2021

Preprint

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Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

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“…Similar to patients with anti-CD20 treated multiple sclerosis (13), some of our patients with LM did not develop a speci c T cell response to the second dose. In contrast, several of the seronegative patients showed an emerging cellular response after dose 3, suggesting a positive effect of a second booster dose despite the absence of humoral response.…”

Section: Discussionsupporting

confidence: 74%

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients with lymphoid malignancies

Ré

Seitz-Polski

Carlès

et al. 2021

Preprint

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BACKGROUND: Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed.METHODS: a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys ® Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen®).RESULTS: Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3.CONCLUSIONSDose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

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Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Cited by 43 publications

References 87 publications

Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination

Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients with lymphoid malignancies

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