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

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Summary We investigated antibody and coronavirus disease 2019 (COVID‐19)‐specific T‐cell mediated responses via ultra‐deep immunosequencing of the T‐cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike‐receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ‐78436735. A total of 56 patients underwent TCR immunosequencing after vaccination. Overall, 86% tested within 6 months of vaccination had detectable spike antibodies. Increasing age, use of anti‐CD38 or anti‐B‐cell maturation antigen therapy, and receipt of BNT162b2 (vs. mRNA‐1273) were associated with lower antibody titres. We observed an increased proportion of TCRs associated with surface glycoprotein regions of the COVID‐19 genome after vaccination, consistent with spike‐specific T‐cell responses. The median spike‐specific T‐cell breadth was 3.11 × 10 −5 , comparable to those in healthy populations after vaccination. Although spike‐specific T‐cell breadth correlated with antibody titres, patients without antibody responses also demonstrated spike‐specific T‐cell responses. Patients receiving mRNA‐1273 had higher median spike‐specific T‐cell breadth than those receiving BNT162b2 ( p = 0.01). Although patients with PCD are often immunocompromised due to underlying disease and treatments, COVID‐19 vaccination can still elicit humoral and T‐cell responses and remain an important intervention in this patient population.