Anti-Spike T-cell and Antibody Responses to SARS-CoV-2 mRNA Vaccines in Patients with Hematologic Malignancies

Lee M. Greenberger, Larry A. Saltzman, Lore M. Gruenbaum, Jun Xu, Sneha T. Reddy, Jonathon W. Senefeld, Patrick W. Johnson, Paul A. Fields, Catherine Sanders, Louis J. DeGennaro, Gwen L. Nichols

Research output: Contribution to journalArticlepeer-review


The anti-spike T-cell and antibody responses to SARS-CoV-2 mRNA vaccines in patients with B-cell malignancies were examined in a real-world setting. A next-generation sequencing (NGS)–based molecular assay was used to assess SARS-CoV-2–specific T-cell responses. After the second dose, 58% (166/284) of seropositive and 45% (99/221) of seronegative patients display anti-spike T cells. The percentage of patients who displayed T-cell response was higher among patients receiving mRNA-1273 vaccines compared with those receiving BNT162b2 vaccines. After the third vaccination, 40% (137/342) of patients seroconverted, although only 22% displayed sufficient antibody levels associated with the production of neutralizing antibodies. 97% (717/738) of patients who were seropositive before the third dose had markedly elevated anti-spike antibody levels. Anti-spike antibody levels, but not T-cell responses, were depressed by B cell–directed therapies. Vaccinated patients with B-cell malignancies with a poor response to SARS-CoV-2 vaccines may remain vulnerable to COVID-19 infections. SIGNIFICANCE: This study represents the first investigation of SARS-CoV-2–specific immune responses to vaccination in a patient registry using an NGS-based method for T-cell receptor repertoire–based analysis combined with anti-spike antibody assessments. Vaccinated patients with B cell–derived hematologic malignancies are likely at higher risk of infection or severe COVID-19.

Original languageEnglish (US)
Pages (from-to)481-489
Number of pages9
JournalBlood cancer discovery
Issue number6
StatePublished - Nov 1 2022
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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