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

Abstract

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. This article is highlighted in the In This Issue feature, p. 476.

Figure 1.

Association between T-cell COVID scores and anti-S antibody levels (A), type of mRNA vaccine (B), and both anti-S antibody levels and type of mRNA vaccine (C). Anti-S antibody levels were assessed by the semiquantitative Elecsys anti-SARS-CoV-2 S enzyme immunoassay using patient sera. COVID scores were obtained as defined in Methods. The horizontal lines represent median, boxes represent interquartile range, and symbols represent each patient. P values were determined using the Wilcox rank-sum test.

Figure 2.

The serological response to second and third vaccinations in individual patients with hematologic malignancies was analyzed for anti-S antibodies as described in the Methods. Individual lines represent each patient. Four types of responses were observed. Those patients who were sero­negative prior to the third vaccination either remained persistent seronegative or seroconverted. Those patients who were seropositive prior to the third vaccination either had an increase in anti-S antibody levels (seroelevated) or had a small decrease in anti-S antibody levels (serodecreased). The red line in each graph represents the median anti-S antibody level.

Figure 3.

The anti-S antibody level in CLL patients was assessed as described in the Methods. Overall response in patients (A); individual dots represent each patient. Response of individual patients before and after the third vaccination for patients with no treatment (B) or treatment (C). Patients treated with BTK inhibitors (D), anti-CD20 antibodies (E), or a combination (F) are shown. Individual lines represent each patient (B–E). Red lines indicate the median response.