Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination

Blixt, Lisa; Gao, Yu; Wullimann, David; Ingelman-Sundberg, Hanna M.; Muschiol, Sandra; Healy, Katie; Bogdanović, Gordana; Pin, Elisa; Nilsson, Peter; Kjellander, Christian; Grifoni, Alba; Sette, Alessandro; Chen, Margaret Sällberg; Ljunggren, Hans‐Gustaf; Buggert, Marcus; Hansson, Lotta; Österborg, Anders

doi:10.1182/blood.2022016815

Cited by 9 publications

(15 citation statements)

References 25 publications

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“…Encouragingly, most patients mounted high post-infection serum and saliva Ab levels, and the serum levels where comparable to those mounted by patients with CLL after 4 vaccine doses. However, the median Ab-response was lower than in another cohort of CLL patients recently analysed by us after having SARS-CoV-2 infection before the Omicron era and thereafter given the mRNA vaccination (10). This hybrid immunity is known to be stronger than after vaccination only, supposedly depending on immunogenic imprinting after the infection (31).…”

Section: Discussionmentioning

confidence: 74%

“…Results are shown as frequency (%) of Spikespeci c cells after subtraction of the paired % of AIM + cells stimulated with DMSO. Negative values after background correction were set to 0.001% to allow graphing with a logarithmic scale with a gating strategy as described earlier (10).…”

Section: T Cell Assaysmentioning

confidence: 99%

“…Additionally, many patients with CLL do not achieve seroconversion upon mRNA vaccination (5-7) with somewhat con icting results regarding T cell immunity (8, 9). In contrast, hybrid immunity, achieved after SARS-CoV-2 infection with early virus variants followed by vaccination, resulted in high anti-Spike antibody (Ab) levels and robust CD8 + T cell responses in patients with CLL (10).…”

Section: Introductionmentioning

confidence: 99%

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Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Ingelman-Sundberg

Blixt

Wullimann

et al. 2023

Preprint

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Patients with chronic lymphocytic leukemia (CLL) were at high risk early in the COVID-19 pandemic. The Omicron SARS-CoV-2 variant is considered less aggressive, but a significant fatality rate was recently reported from CLL register studies. Here we report on Omicron hybrid immunity in CLL after vaccinations against SARS-CoV-2 followed by disease. Post-infection systemic and mucosal immunity against SARS-CoV-2 were analyzed in patients with CLL (n = 38) during the Omicron BA.1/BA.2 time-period. Most patients (30/38, 79%) had received 3 to 4 vaccine doses, yet median anti-Spike antibody titers were 0 U/mL (range 0–6,528) at the onset of infection. Significantly elevated serum antibody levels were observed post-infection (p = 0.0027 vs baseline) to a median of 3,145 U/mL (range 0->25 000) which correlated with inhibition of Spike-ACE2 binding. Low convalescent IgA responses were noted in both saliva and serum in patients with ongoing BTKi/BCL-2i therapy compared with early-stage untreated patients (p = 0.010; p = 0.051). Post-Omicron CD4 + and CD8 + T cell responses were observed at levels similar to those of healthy donors. Forty-seven percent of the patients required hospitalization but there was only one possibly related death. Broad immunity was observed in patients with CLL following Omicron infection. Impaired mucosal immunity during BTKi therapy requires further studies.

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Section: Discussionmentioning

confidence: 74%

Section: T Cell Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Ingelman-Sundberg

Blixt

Wullimann

et al. 2023

Preprint

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“…In total, 60 studies were included for data analysis on booster COVID-19 vaccination, 43 studies reported on the immune response of a total of 4754 patients with a diagnosis of hematological malignancy, and 22 studies determined immune seroconversion in 2440 patients with solid tumors [ 78 , 79 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ,…”

Section: Resultsmentioning

confidence: 99%

“… Pooled EffectSize (ES) for the immune seroconversion rates of patients with hematological malignancies after the third dose of COVID-19 vaccine [ 28 , 74 , 85 , 87 , 88 , 89 , 91 , 92 , 93 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 104 , 105 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 114 , 116 , 117 , 118 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 134 , 135 ]. …”

Section: Figurementioning

confidence: 99%

Adult Patients with Cancer Have Impaired Humoral Responses to Complete and Booster COVID-19 Vaccination, Especially Those with Hematologic Cancer on Active Treatment: A Systematic Review and Meta-Analysis

Liatsou

Ntanasis‐Stathopoulos

Lykos

et al. 2023

Cancers

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The exclusion of patients with cancer in clinical trials evaluating COVID-19 vaccine efficacy and safety, in combination with the high rate of severe infections, highlights the need for optimizing vaccination strategies. The aim of this study was to perform a systematic review and meta-analysis of the published available data from prospective and retrospective cohort studies that included patients with either solid or hematological malignancies according to the PRISMA Guidelines. A literature search was performed in the following databases: Medline (Pubmed), Scopus, Clinicaltrials.gov, EMBASE, CENTRAL and Google Scholar. Overall, 70 studies were included for the first and second vaccine dose and 60 studies for the third dose. The Effect Size (ES) of the seroconversion rate after the first dose was 0.41 (95%CI: 0.33–0.50) for hematological malignancies and 0.56 (95%CI: 0.47–0.64) for solid tumors. The seroconversion rates after the second dose were 0.62 (95%CI: 0.57–0.67) for hematological malignancies and 0.88 (95%CI: 0.82–0.93) for solid tumors. After the third dose, the ES for seroconversion was estimated at 0.63 (95%CI: 0.54–0.72) for hematological cancer and 0.88 (95%CI: 0.75–0.97) for solid tumors. A subgroup analysis was performed to evaluate potential factors affecting immune response. Production of anti-SARS-CoV-2 antibodies was found to be more affected in patients with hematological malignancies, which was attributed to the type of malignancy and treatment with monoclonal antibodies according to the subgroup analyses. Overall, this study highlights that patients with cancer present suboptimal humoral responses after COVID-19 vaccination. Several factors including timing of vaccination in relevance with active therapy, type of therapy, and type of cancer should be considered throughout the immunization process.

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The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses

da Silva Antunes,

Weiskopf,

Sidney

et al. 2023

Current Protocols

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Epitopes recognized by T cells are a collection of short peptide fragments derived from specific antigens or proteins. Immunological research to study T cell responses is hindered by the extreme degree of heterogeneity of epitope targets, which are usually derived from multiple antigens; within a given antigen, hundreds of different T cell epitopes can be recognized, differing from one individual to the next because T cell epitope recognition is restricted by the epitopes’ ability to bind to MHC molecules, which are extremely polymorphic in different individuals. Testing large pools encompassing hundreds of peptides is technically challenging because of logistical considerations regarding solvent‐induced toxicity. To address this issue, we developed the MegaPool (MP) approach based on sequential lyophilization of large numbers of peptides that can be used in a variety of assays to measure T cell responses, including ELISPOT, intracellular cytokine staining, and activation‐induced marker assays, and that has been validated in the study of infectious diseases, allergies, and autoimmunity. Here, we describe the procedures for generating and testing MPs, starting with peptide synthesis and lyophilization, as well as a step‐by‐step guide and recommendations for their handling and experimental usage. Overall, the MP approach is a powerful strategy for studying T cell responses and understanding the immune system's role in health and disease. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Generation of peptide pools (“MegaPools”)Basic Protocol 2: MegaPool testing and quantitation of antigen‐specific T cell responses

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Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination

Cited by 9 publications

References 25 publications

Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Systemic and mucosal adaptive immunity to SARS-CoV-2 during the Omicron wave in patients with chronic lymphocytic leukemia

Adult Patients with Cancer Have Impaired Humoral Responses to Complete and Booster COVID-19 Vaccination, Especially Those with Hematologic Cancer on Active Treatment: A Systematic Review and Meta-Analysis

The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses

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