Antibody and T‐cell responses by ultra‐deep T‐cell receptor immunosequencing after <scp>COVID</scp>‐19 vaccination in patients with plasma cell dyscrasias

Chung, Alfred; Banbury, Barbara L.; Vignali, Marissa; Huang, Chiung‐Yu; Asoori, Sireesha; Johnson, Rachel K.; Kurtz, Theodore W.; Arora, Shagun; Wong, Sandy W.; Shah, Nina; Martin, Thomas G.; Wolf, Jeffrey L.

doi:10.1111/bjh.18434

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…However, our observation of a largely preserved T-cell response after baseline vaccination in the patients with multiple myeloma without a difference from the healthy controls matches the majority of previous reports [21][22][23][24][25].…”

Section: Discussionsupporting

confidence: 92%

Humoral and cellular BNT162b2 mRNA-based booster vaccine-induced immunity in patients with multiple myeloma and persistence of neutralising antibodies: results of a prospective single-centre cohort study

Silzle,

Kahlert,

Albrich

et al. 2023

Swiss Med Wkly

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BACKGROUND: Currently available messenger ribonucleic acid (mRNA)-based vaccines against coronavirus disease (COVID-19) have been shown to be effective even in highly immunocompromised hosts, including patients with multiple myeloma. However, vaccination failure can be observed in all patient groups. METHODS: This prospective study longitudinally assessed the humoral and cellular responses to a third booster dose of BNT162b2 mRNA-based vaccine in patients with myeloma (n = 59) and healthy controls (n = 22) by measuring the levels of anti-spike (S) antibodies (electro-chemiluminescence immunoassay) including neutralising antibodies and specific T-cells (enzyme-linked immunospot assay) following booster administration. RESULTS: The third booster dose showed a high immunogenicity on the serological level among the patients with multiple myeloma (median anti-S level = 41 binding antibody units [BAUs]/ml pre-booster vs 3902 BAU/ml post-booster, p <0.001; increase in the median neutralising antibody level from 19.8% to 97%, p <0.0001). Four of five (80%) patients with a complete lack of any serological response (anti-S immunoglobulin level <0.8 BAU/ml) after two vaccine doses developed detectable anti-S antibodies after booster vaccination (median anti-S level = 88 BAU/ml post-booster). T-cell responses were largely preserved among the patients with multiple myeloma with no difference from the healthy controls following baseline vaccination (median spot-forming units [SFU]/106 of peripheral blood mononuclear cells = 193 vs 175, p = 0.711); these responses were augmented significantly after booster administration among the patients with multiple myeloma (median SFU/106 of peripheral blood mononuclear cells = 235 vs 443, p <0.001). However, the vaccination responses remained highly heterogeneous and diminished over time, with insufficient serological responses occurring even after booster vaccination in a few patients irrespective of the treatment intensity. CONCLUSIONS: Our data demonstrate improvements in humoral and cellular immunity following booster vaccination and support the assessment of the humoral vaccine response in patients with multiple myeloma until a threshold for protection against severe COVID-19 is validated. This strategy can allow the identification of patients who might benefit from additional protective measures (e.g. pre-exposure prophylaxis via passive immunisation).

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Section: Discussionsupporting

confidence: 92%

Humoral and cellular BNT162b2 mRNA-based booster vaccine-induced immunity in patients with multiple myeloma and persistence of neutralising antibodies: results of a prospective single-centre cohort study

Silzle,

Kahlert,

Albrich

et al. 2023

Swiss Med Wkly

View full text Add to dashboard Cite

show abstract

“…Alternatively, differences in formulation or in the prime-boost timing of the 2 vaccines could contribute to differences in efficacy. The vaccine type had much less effect on the quality of the T cell response, and we could not confirm a previously reported higher T cell response to the Moderna compared with the Pfizer vaccine (44).…”

Section: Medication Use Was a Major Determinant Of Low Antibody Respo...contrasting

confidence: 96%

Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases

Anderson,

Powell,

Yang

et al. 2024

JCI Insight

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Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti–spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell–depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti–spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti–type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2–related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

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“…T-cell responses against SARS-CoV-2 variants of concern may be important to attenuate the disease severity in breakthrough infections [ 126 ]. Another point to consider is that spike-specific T-cell responses may become evident even in seronegative patients following vaccination [ 97 , 119 , 127 ], which underlines the importance of booster vaccination for supporting cellular immunity in these patients.…”

Section: Methodsmentioning

confidence: 99%

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

et al. 2023

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In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6–12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.

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Antibody and T‐cell responses by ultra‐deep T‐cell receptor immunosequencing after COVID‐19 vaccination in patients with plasma cell dyscrasias

Cited by 7 publications

References 39 publications

Humoral and cellular BNT162b2 mRNA-based booster vaccine-induced immunity in patients with multiple myeloma and persistence of neutralising antibodies: results of a prospective single-centre cohort study

Humoral and cellular BNT162b2 mRNA-based booster vaccine-induced immunity in patients with multiple myeloma and persistence of neutralising antibodies: results of a prospective single-centre cohort study

Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

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