Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma

Aleman, Adolfo; Upadhyaya, Bhaskar; Tuballes, Kevin; Kappes, Katerina; Gleason, Charles; Beach, Katherine F.; Agte, Sarita; Srivastava, Komal; Pvi,; Oekelen, Oliver Van; Barcessat, Vanessa; Bhardwaj, Nina; Kim‐Schulze, Seunghee; Gnjatic, Sacha; Brown, Brian D.; Cordon‐Cardo, Carlos; Krammer, Florian; Mérad, Miriam; Jagannath, Sundar; Wajnberg, Ania; Simon, Viviana; Parekh, Samir

doi:10.1016/j.ccell.2021.09.015

Cited by 68 publications

(78 citation statements)

References 10 publications

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“…Another intriguing finding of this study is the fact that the moderate humoral responses were strictly accompanied by T cellular memory responses, which is in accordance with previous findings, that in the majority of vaccine non-responders also T cell responses are absent [ 21 ]. While it could have been assumed that T cell responses could have established themselves even in the absence of functional B cells, this was not what we found here.…”

Section: Discussionsupporting

confidence: 92%

“…In contrast, while CD3 + CD8 + T cells of the control subject strongly neo-expressed CD25 and CD69 upon incubation with S-peptide mix, this was not evident with CD3 + CD8 + T cells of the patient, indicating a potential scar in the respective repertoire. Recent reports confirmed these findings, showing that more patients and healthy controls mounted an efficient CD4+ T cell as compared to a CD8+ T cell response [ 21 ].…”

Section: Discussionmentioning

confidence: 67%

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Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

et al. 2022

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Background: Prophylactic vaccination against infectious diseases may induce a state of long-term protection in the otherwise healthy host. However, the situation is less predictable in immunocompromised patients and may require adjustment of vaccination schedules and/or basic therapy. Methods: A patient in full remission of multiple myeloma since the last three years and on long-term maintenance therapy with pomalidomide, a drug inhibiting angiogenesis and myeloma cell growth, was vaccinated twice with Comirnaty followed by two vaccinations with Vaxzevria. Seroconversion and SARS-CoV-2-specific cellular responses were monitored. Results: No signs of seroconversion or T cellular memory were observed after the first “full immunization” with Comirnaty. Consequently, long-term-maintenance therapy with Pomalidomide was stopped and two additional shots of Vaxzevria were administered after which the patient seroconverted with Spike(S)-protein specific antibody levels reaching 49 BAU/mL, mild S-peptide pool-specific T cell proliferation, effector cytokine production (IL-2, IL-13), and T cellular activation with increased numbers of CD3+CD4+CD25+ T cells as compared to vaccinated and non-vaccinated control subjects. However, despite suspension of immunosuppression and administration of in total four consecutive heterologous SARS-CoV-2 vaccine shots, the patient did not develop neutralizing RBD-specific antibodies. Conclusions: Despite immunomonitoring-based adjustment of vaccination and/or therapy schedules vaccination success, with clear correlates of protection, the development of RBD-specific antibodies could not be achieved in the immunocompromised patient with current SARS-CoV-2 vaccines. Thus, our report emphasizes the need for improved active and passive immunization strategies for SARS-CoV-2 infections.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 67%

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

et al. 2022

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“…Hematological malignancies were associated with lower vaccine response than solid malignancies, consistent with other reports 15,16,20,22,26,27 . Interestingly, patients with a history of B cell lymphomas or plasma cell diseases, not on ISMT, had low rates of humoral response but high rates of cellular response, while those with a history of acute leukemias, such as B lymphoblastic leukemia, had high rates of both humoral and cellular response.…”

supporting

confidence: 91%

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

Yang

Costales

Ramanathan

et al. 2022

Preprint

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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.

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“…23,24,33,34 Until now, only two groups described variable results on the antigen-specific cellular responses in the MM setting. In fact, Aleman et al 11 highlighted that fully vaccinated seronegative MM patients had a reduction in the percentage of spike-specific CD4 + T cells compared to the seropositive patients. On the other hand, another study on MM patients showed a significant lower percentage of spike-specific CD8 + INF-γ + T cells in the seronegative group.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 In addition, MM patients treated with anti-CD38 or anti-B-cell maturation antigen (BCMA) antibodies, seem not to develop anti-SARS-CoV-2 antibodies or have insufficient response even after full vaccination. 9,10 However, very few data are actually available about the cellular response to SARS-CoV-2 mRNA vaccination 11 and the efficacy of the mRNA vaccine, including the booster dose, to the different SARS-CoV-2 variant characterized by mutations encoding for the spike protein. 12 Since November 2021, the B.1.1.529 (Omicron) variant has rapidly become dominant globally.…”

Section: Introductionmentioning

confidence: 99%

Impact of Omicron variant on the response to SARS-CoV-2 mRNA Vaccination in multiple myeloma

Storti

Marchica

Vescovini

et al. 2022

Preprint

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Multiple myeloma (MM) patients may have a reduced response to vaccination due to immunodeficiency. The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of spike variants, including the emerging Omicron one, are still unclear and have been investigated in this study in a cohort of MM patients and those with pre-malignant monoclonal gammopathies. Firstly, we have shown that MM patients with relapsed-refractory disease (MMR) had a reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 mRNA full vaccination. Interestingly, all the analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and in smoldering MM too. Moreover, lower spike-specific IL-2-producing CD4+ T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing-CD8+ T cells were found in MM patients as compared to MGUS. Finally, we found that booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. On the other hand, in MMR patients, Omicron retain a negative impact on neutralizing ability, suggesting these patients need to be considered still at risk of Omicron SARS-CoV-2 infection with a clinically relevant disease.

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Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma

Cited by 68 publications

References 10 publications

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

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

Impact of Omicron variant on the response to SARS-CoV-2 mRNA Vaccination in multiple myeloma

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