scholarly journals Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies

Cancer Cell ◽  
2021 ◽  
Author(s):  
Lee M. Greenberger ◽  
Larry A. Saltzman ◽  
Jonathon W. Senefeld ◽  
Patrick W. Johnson ◽  
Louis J. DeGennaro ◽  
...  
Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3105-3105
Author(s):  
Roberto Bellucci ◽  
Meagan Gallagher ◽  
Sabine Oertelt ◽  
Emmanuel Zorn ◽  
Edwin P. Alyea ◽  
...  

Abstract Although, the effectiveness of allogeneic hematopoietic stem cell transplantation (HSCT) is, in large part, due to the destruction of recipient malignant cells by donor immune cells, the antigenic targets of this response in most patients are not well defined. In previous studies we demonstrated that patients with multiple myeloma (MM) who achieved a complete response after HSCT and donor lymphocyte infusion (DLI) developed high titer antibodies to a variety of antigens expressed by myeloma cells. Dihydrolipoamide acetyltransferase, the E2 component of the pyruvate dehydrogenase complex (PDC-E2) was one of the antigens identified in this screen. Importantly PDC-E2 is the immunodominant auto-antigen in primary biliary cirrhosis (PBC), a liver autoimmune disease in which greater than 95% of patients develop auto-antibodies against the inner lipoyl domain of this mitochondrial antigen. To further characterize the antibody response against PDC-E2 after allogeneic HSCT, we developed a sensitive ELISA to measure antibody responses to GST-PDC-E2 fusion protein. PDC-E2 antibodies following HSCT were compared to 52 normal donors and 50 patients with PBC. All samples were tested at 1:50 or 1:100 dilution. PDC-E2 antibodies were not detected in 20 patients with MM at the time of diagnosis, 10 patients with hematologic malignancies after allogeneic HSCT who did not receive DLI and 10 patients with chronic graft-versus-host disease (GVHD). However, when screening patients who achieved complete remission after DLI, PDC-E2 antibodies were detecting in 3 out of 10 patients with MM, 1 out of 5 patients with chronic myelocytic leukemia (CML) and 1 out of 2 patients with chronic lymphocytic leukemia (CLL). Although some of these patients developed GVHD, none developed chronic liver disease. In each case, PDC-E2 antibodies were only detectable after DLI and not pre-HSCT or pre-DLI. In 2 patients with particulary high titer antibodies (detectable down to 1:10,000 dilution) anti-PDC-E2 persisted for more than 2 years post-DLI and the dominant Ig subclasses at all time points were IgG1 and IgG2. The specificity of PDC-E2 antibodies post-DLI was also tested by ELISA against a panel of 85 overlapping peptides representing the entire amino acid sequence of PDC-E2 and by western blot against 2 common mitochondrial auto-antigens, branched-chain alpha-keto acid dehydrogenase (BCKD) and 2-oxoglutarate dehydrogenase (ODGC). Post-DLI sera were not reactive with BCKD or ODGC and most samples specifically recognized 2 peptides located in the E2 catalytic domain of PDC-E2. In contrast, serum from PBC patients had a different pattern of reactivity and were primarily directed against peptides in the inner lipoyl domain of PDC-E2. In conclusion, we demonstrate that patients with hematologic malignancies who achieve complete remission following DLI frequently develop allogeneic antibody responses directed against one of the most common auto-antigens in PBC. However, the epitope specificity of the antibody response following allogeneic HSCT is distinct and is not associated with chronic liver disease.


Cancer Cell ◽  
2021 ◽  
Vol 39 (10) ◽  
pp. 1297-1299 ◽  
Author(s):  
Lee M. Greenberger ◽  
Larry A. Saltzman ◽  
Jonathon W. Senefeld ◽  
Patrick W. Johnson ◽  
Louis J. DeGennaro ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1999-1999
Author(s):  
Panayotis Kaloyannidis ◽  
Varnavas Konstantinou ◽  
Elisavet Georgiadou ◽  
Fani Zervou ◽  
Ioannis Batsis ◽  
...  

Abstract Abstract 1999 Infections are major barriers for a favorable outcome following stem cell transplantation (SCT) and their prevention is a significant task in the clinical practice. Vaccinations are well established strategies to reduce the risk of vaccine-preventable infection after SCT. The effectiveness of timely vaccination is subject to many factors including the patient's immune reconstitution. Consequently, the response to vaccination may also be an indirect marker for assessing immune function. Although some reports have demonstrated that the type of transplant may affect the response to vaccines, the European Group for Blood and Marrow Transplantation (EBMT), for practical reasons, recommends identical vaccination programs for allo- and auto SCT. Hepatitis B virus (HBV) can cause severe and sometimes fatal hepatitis after SCT and therefore all anti-HBs negative transplant recipients should receive vaccination against HBV post SCT. Although very limited published data exist, the general aspect is that the immune system rapidly recovers following autoSCT and so far, autografted patients are considered to have similar antibody response to healthy individuals. The vaccination programs for HBV in healthy population are: i) three doses at 0, 1, and 6 months, or ii) four doses at 0, 1, 2 and 12 months for high risk individuals. The reported response rate is 15% after the 1st and 80–89% after the 2nd dose. The EBMT recommends 3 doses (0, 1, and 6 months) for both auto and allo recipients. In this study we evaluated the anti-HBs response of 36 autografted recipients for hematologic malignancies, vaccinated against HBV with a recombinant DNA vaccine (EngerixÒ20mcgr, GlaxoSmithKline). All patients achieved or maintained complete response (CR), and received no other therapy after SCT. Their median age was 34(14–55) years and they had received 2(2–7) lines of chemotherapy prior to SCT. BEAM was the conditioning regimen for the majority of the patients (26/36). No patient was immunized for HBV prior to SCT. The median interval from the time of transplant to the first dose of the vaccine was 5.5 (2–20.5) years. The median CD34+ and CD3+ infused cells were 4.5×106/kg and 1.96×108/kg, respectively. The engraftment was successful and the reconstitution (cells >500/mm3) for neutrophils was observed at day +11 while for lymphocytes at day +15. After day +100 the median counts of CD4+, CD8+, NK and B lymphocytes were 287, 909, 273 and 154/ml, respectively. According to our study's vaccination schedule, patients who achieved protective (>10mIU/ml) anti-HBs titers after the 2nd dose received the 3rd dose at 6 months (0, 1 and 6 months schedule) while the non-responders received two more doses (0, 1, 2 and 12 months schedule). After the 1st dose only 1/36 patients (3%) had protective response. This percentage reached to 17% after the 2nd dose (5/30 evaluated patients). Seven of nine (77%) patients, developed >10 IU/l anti-HBs titers after the 3rd dose. In a univariate (t-test) and multivariate (logistic regression) analysis the following factors were evaluated: sex, age, lines of therapies, number of infused CD34+ and CD3+ cells, time to engraftment for neutrophils and lymphocytes and the interval from SCT to vaccination. No factor was proven to be significant in terms of achieving protective anti-HBs titers after the 2nd dose of vaccination, probably due to the number of evaluated patients. According to the published data, this ongoing study represents the largest series of patients post autoSCT studied for anti-HBs response after vaccination against HBV. The low response rates we observed following the 2nd dose (only 17% vs. 80–89% that has been reported for healthy people) may suggest that autografted patients possibly have a long lasting immune impairment and hence an intensified vaccination program is needed for this group of patients. Undoubtedly, definitive conclusions will be drawn from studies with larger series of patients. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 185-185
Author(s):  
Lee M Greenberger ◽  
Larry A Saltzman ◽  
Jonathon W Senefeld ◽  
Patrick W Johnson ◽  
Louis J DeGennaro ◽  
...  

Abstract Immunosuppressed patients may be at high risk for breakthrough COVID-19 infection despite SARS-CoV-2 vaccination, due to an inadequate or negligible antibody response. Based on data from the Leukemia & Lymphoma Society (LLS) National Registry, 25% of patients with hematologic malignancies do not produce anti-Spike protein antibodies in response to mRNA vaccines, with B-cell malignancy patients at highest risk (Greenberger et al, 2021, Cancer Cell, on-line). While studies of T-cell immunity, antibody cocktails, and booster vaccinations are underway, some patients have elected to receive an additional "booster" vaccination after a full course of SARS-CoV-2 vaccination. The LLS National Registry (NCT04794387) has collected Patient Reported Outcomes and serology from 3300 patients with hematologic malignancies. This study was approved by the Western Institutional Review Board, and participants provided informed consent electronically. As of July 2021, the Registry includes 24 patients who obtained a 3 rd vaccination after full vaccination with mRNA vaccines. Twenty of these patients were seronegative >14 days post 2 nd vaccination (as measured by the Roche Elecsys assay). Four patients had low positive serology results. All patients were nucleocapsid antibody negative. Patient ages ranged from 51-79 years. Eleven had chronic lymphocytic leukemia (CLL), 7 non-Hodgkin's lymphoma (NHL), 5 Waldenstrom's macroglobulinemia (WM), and 1 multiple myeloma (MM). Six patients were not currently on anti-B cell therapy, 11 had received anti-CD20 therapy (8 within the last 6 months), 6 had received Bruton's tyrosine kinase (BTK) inhibitors within the last 6 months, and 1 patient had recently received chemotherapy. The booster vaccinations were obtained between April and June 2021, 21 to 114 days after completing the initial vaccination series between January and April 2021. Serology was performed 12-61 days post-booster vaccination. Fifteen patients received a heterologous adenovirus vaccine. Four patients received a heterologous mRNA vaccine, 5 patients received a homologous mRNA vaccine. Descriptive results are shown on the following table. All patients (4) who had some level of antibody response to the initial vaccines had an augmented antibody response after a booster (i.e. sero-enhanced). Patients who had prior anti-CD20 often failed to seroconvert after booster vaccination. Only 2 of 8 patients who received anti-CD20 antibody treatment in the 6 months prior to vaccination seroconverted after booster vaccination. Two out of 3 seronegative patients receiving anti-CD20 therapy in the last 2 years (but > 6 months) seroconverted after the booster. One patient with follicular lymphoma who received anti-CD20 therapy in 2019 remained seronegative despite a prolonged duration without therapy. Of the 6 seronegative patients taking BTK inhibitors, 3 seroconverted after the booster. Two of the 3 remaining seronegative patients were taking concomitant anti-CD20 therapy. Of the 4 seronegative patients not currently taking anti-B cell therapy, 3 seroconverted while one patient who currently required intravenous immunoglobulin remained seronegative. A patient currently receiving chemotherapy also did not respond to a booster. In this limited set of patients there was no evident pattern of antibody response amongst patients who received homologous versus heterologous vaccine nor between disease types. While anti-CD20 therapy appeared to reduce antibody response to booster vaccination, there was substantial heterogeneity. Although many patients with B-cell malignancies did not mount a robust response to full mRNA vaccine series, several patients demonstrated an antibody response to the booster vaccination. Clinical trials are needed to further understand who can benefit from a booster strategy as well as define the safety of the approach. The LLS Registry includes collection of Electronic Health Records, which will allow us to more specifically evaluate timing and dosage of boosters, the influence of prior therapeutics, as well as health and safety outcomes to better guide patients and physicians through the COVID-19 pandemic. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Booster vaccination (after full vaccination) using BNT162b2, mRNA-1273, or Ad26.COV2.S


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