tetano
Editor, Senior Moderator
Br J Haematol
. 2022 Aug 30.
doi: 10.1111/bjh.18434. Online ahead of print.
Antibody and T-cell responses by ultra-deep T-cell receptor immunosequencing after COVID-19 vaccination in patients with plasma cell dyscrasias
Alfred Chung[SUP] 1 [/SUP], Barbara Banbury[SUP] 2 [/SUP], Marissa Vignali[SUP] 2 [/SUP], Chiung-Yu Huang[SUP] 3 [/SUP], Sireesha Asoori[SUP] 1 [/SUP], Rachel Johnson[SUP] 4 [/SUP], Theodore Kurtz[SUP] 5 [/SUP], Shagun Arora[SUP] 1 [/SUP], Sandy W Wong[SUP] 1 [/SUP], Nina Shah[SUP] 1 [/SUP], Thomas G Martin[SUP] 1 [/SUP], Jeffrey L Wolf[SUP] 1 [/SUP]
Affiliations
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[SUP]-5[/SUP] , 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.
. 2022 Aug 30.
doi: 10.1111/bjh.18434. Online ahead of print.
Antibody and T-cell responses by ultra-deep T-cell receptor immunosequencing after COVID-19 vaccination in patients with plasma cell dyscrasias
Alfred Chung[SUP] 1 [/SUP], Barbara Banbury[SUP] 2 [/SUP], Marissa Vignali[SUP] 2 [/SUP], Chiung-Yu Huang[SUP] 3 [/SUP], Sireesha Asoori[SUP] 1 [/SUP], Rachel Johnson[SUP] 4 [/SUP], Theodore Kurtz[SUP] 5 [/SUP], Shagun Arora[SUP] 1 [/SUP], Sandy W Wong[SUP] 1 [/SUP], Nina Shah[SUP] 1 [/SUP], Thomas G Martin[SUP] 1 [/SUP], Jeffrey L Wolf[SUP] 1 [/SUP]
Affiliations
- PMID: 36041779
- DOI: 10.1111/bjh.18434
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[SUP]-5[/SUP] , 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.