Probing the underlying mechanisms of immune dysfunction in Chronic lymphocytic leukemia

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With a median age at diagnosis of 70 years, chronic lymphocytic leukemia (CLL) is the most common form of leukemia in Western nations and primarily affects the elderly. Following SARS-CoV-2 mRNA immunization, patients with CLL exhibit lower seroconversion rates and binding antibody (Ab) and neutralising antibody (NAb) titers than healthy persons.

To comprehend the mechanisms behind the immunological dysfunction brought on by CLL, a recent study analyzed the humoral and cellular responses mediated by vaccines. Researchers looked at how patients with different levels of illness progression responded to the SARS-CoV-2 mRNA vaccine in terms of their humoral and cellular immune systems.

95 CLL patients were enrolled in outpatient clinics, and 30 healthy controls were recruited on a rolling basis from the community. Both the BNT162b2 and the mRNA-1273 vaccines were administered twice to each individual. The SARS-CoV-2 Wu-01 spike protein is encoded in both vaccines.

Then, within three months of the most recent vaccination, researchers obtained blood samples and processed them to produce plasma and peripheral blood mononuclear cells (PBMCs), respectively. None of the individuals disclosed having previously contracted SARS-CoV-2. According to the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) recommendations, CLL patients had their clinical features determined by looking backward through electronic medical data.

Sixty-one CLL patients and 27 healthy controls received 2 doses of the Pfizer-BioNTech BNT162b2 vaccine, while 34 CLL patients and 3 healthy controls received 2 doses of the Moderna mRNA-1273 vaccine.

Scientists noted, “Testing plasma samples for SARS-CoV-2 anti-spike and receptor-binding domain Abs by enzyme-linked immunosorbent assay (ELISA), we found that all healthy controls seroconverted to both antigens, while CLL patients had lower response rates (68% and 54%) as well as lower median titers.”

“By examining binding and neutralizing antibody responses, we found a subset of mostly treatment-naive vaccinees who could still mount de novo responses to SARS-CoV-2 antigens, albeit at titers lower than healthy controls.”

In contrast, a second group of CLL vaccine recipients exhibited spike-binding antibodies that largely responded with the SARS-CoV-2 S2 subunit but could not produce SARS-CoV-2 neutralizing antibodies (S+NAb-, yellow). Although the vaccine might have caused these antibodies, it is much more likely that they are recall reactions to anti-HCoV antibodies that were present in the past and cross-reacted with conserved S2 epitopes.

The third group of CLL vaccinees had no detectable SARS-CoV-2 antibodies. This indicates an inability to mount de novo as well as recall responses. Most of these individuals required IVIg prophylaxis, demonstrating they were the most immune compromised. Thus, SARS-CoV-2 vaccination exposed a progressive loss of immune functions in CLL patients, including those not meeting the criteria for therapy, with preexisting memory being preserved longer than the capacity to respond to new antigens.

“A key finding in our study was the demonstration of superior neutralizing antibody responses in CLL patients who received the mRNA-1273 vaccine. This observation is consistent with previous findings of improved seroconversion rates, binding antibody titers, and T-cell activity for mRNA-1273 vaccinees in studies of other hematologic malignancies, including CLL.”

Journal Reference:

  1. Qin K, Honjo K, Sherrill-Mix S, Liu W, Stoltz RM, Oman AK, et al. (2023) Exposure of progressive immune dysfunction by SARS-CoV-2 mRNA vaccination in patients with chronic lymphocytic leukemia: A prospective cohort study. PLoS Med 20(6): e1004157. DOI: 10.1371/journal.pmed.1004157

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