Abstract
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.
Keywords: COVID-19; T-cell receptor; immune; immunization; myeloma; vaccines.
【저자키워드】 COVID-19, immunization, immune, Vaccines., Myeloma, T-cell receptor, 【초록키워드】 coronavirus disease, antibodies, Antibody testing, vaccination, therapy, Vaccines, antibody, mRNA vaccine, mRNA-1273, Antibody Response, T-cell Response, Genome, Intervention, underlying disease, Population, Antigen, Surface glycoprotein, BNT162b2, Region, COVID-19 vaccination, Immunoglobulin, response, Patient, Immunocompromised, plasma, age, T-cell, TCR, breadth, dose, humoral, maturation, antibody titres, anti-CD38, binding domain, patient population, JNJ-78436735, Cell, Spike-specific T-cell responses, dyscrasia, initial, tested, proportion, healthy, investigated, detectable, receiving, median, demonstrated, correlated, elicit, comparable, Increasing, of BNT162b2, spike-specific T-cell, 【제목키워드】 T-cell Response, COVID-19 vaccination, Patient, plasma, Cell, dyscrasia,