Dataset Information

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.

SUBMITTER: Greenberger LM

PROVIDER: S-EPMC9894565 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Greenberger Lee M LM Saltzman Larry A LA Gruenbaum Lore M LM Xu Jun J Reddy Sneha T ST Senefeld Jonathon W JW Johnson Patrick W PW Fields Paul A PA Sanders Catherine C DeGennaro Louis J LJ Nichols Gwen L GL

Blood cancer discovery 20221101 6

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 co ...[more]

PMID: 36074641

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Project description:Studies examining antibody responses by vaccine brand are lacking and may be informative for optimizing vaccine selection, dosage, and regimens. The purpose of this study is to assess IgG antibody responses following immunization with BNT162b2 (30 μg mRNA) and mRNA-1273 (100 μg mRNA) vaccines. A cohort of clinicians at a nonprofit organization is being assessed clinically and serologically following immunization with BNT162b2 or mRNA-1273. IgG responses were measured at the Remington Laboratory by an IgG assay against the SARS-CoV-2 spike protein-receptor binding domain. Mixed-effect linear (MEL) regression modeling was used to examine whether the SARS-CoV-2 IgG level differed by vaccine brand, dosage, or number of days since vaccination. Among 532 SARS-CoV-2 seronegative participants, 530 (99.6%) seroconverted with either vaccine. After adjustments for age and gender, MEL regression modeling revealed that the average IgG antibody level increased after the second dose compared to the first dose (P < 0.001). Overall, titers peaked at week 6 for both vaccines. Titers were significantly higher for the mRNA-1273 vaccine on days 14 to 20 (P < 0.05), 42 to 48 (P < 0.01), 70 to 76 (P < 0.05), and 77 to 83 (P < 0.05) and higher for the BNT162b2 vaccine on days 28 to 34 (P < 0.001). In two participants taking immunosuppressive drugs, the SARS-CoV-2 IgG antibody response remained negative. mRNA-1273 elicited higher IgG antibody responses than BNT162b2, possibly due to the higher S-protein delivery. Prospective clinical and serological follow-up of defined cohorts such as this may prove useful in determining antibody protection and whether differences in antibody kinetics between the vaccines have manufacturing relevance and clinical significance. IMPORTANCE SARS-CoV-2 vaccines using the mRNA platform have become one of the most powerful tools to overcome the COVID-19 pandemic. mRNA vaccines enable human cells to produce and present the virus spike protein to their immune system, leading to protection from severe illness. Two mRNA vaccines have been widely implemented, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech). We found that, following the second dose, spike protein antibodies were higher with mRNA-1273 than with BNT162b2. This is biologically plausible, since mRNA-1273 delivers a larger amount of mRNA (100 μg mRNA) than BNT162b2 (30 μg mRNA), which is translated into spike protein. This difference may need to be urgently translated into changes in the manufacturing process and dose regimens of these vaccines.

Dataset Information

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

Significance

Publications

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

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