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Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia
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- Andersson, Maria (author)
- Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Hematol, Stockholm, Sweden.
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- Wu, Jinghua (author)
- Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden.
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- Wullimann, David (author)
- Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden.
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- Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Univ Hosp Solna, Dept Hematol, Stockholm, Sweden. Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden. (creator_code:org_t)
- Elmer Press, Inc. 2023
- 2023
- English.
- In: Journal of Hematology. - : Elmer Press, Inc.. - 1927-1212 .- 1927-1220. ; 12:4, s. 170-175
- Journal article (peer-reviewed)
Abstract
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- Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination.Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides.Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors.Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- CLL
- Zanubrutinib
- SARS-CoV-2
- Immunity
- Vaccination
Publication and Content Type
- ref (subject category)
- art (subject category)
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