Cellular and humoral immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in patients with hematologic malignancies

Abstract

Recent studies have demonstrated a suboptimal humoral response to SARS-CoV-2 mRNA vaccines in patients diagnosed with hematologic malignancies, however data about cellular immunogenicity is scarce. In this study we aimed to evaluate both the humoral and cellular immunogenicity one month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by the Elecsys and LIAISON Anti-SARS-CoV-2 S assay while T-cell response was assessed by Interferon-Gamma-Release-immuno-Assay technology. Overall, 76.3% (184/241) of patients developed humoral immunity and the cellular response rate was 79% (184/233). Hypogammaglobulinemia, lymphopenia, active hematological treatment and anti-CD20 therapy during the last 6 months were associated with an inferior humoral response. Conversely, age over 65 years, active disease, lymphopenia and immunosuppressive treatment for GvHD were associated with an impaired cellular response. A significant dissociation between humoral and cellular response was observed in patients treated with anti-CD20 therapy, being the humoral response of 17.5% whereas the cellular response was 71.1%. In these patients B-cell aplasia was confirmed while T cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients under immunosuppressive treatment for GvHD, while only 52.4% had cellular response. The cellular and humoral response to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematological malignancies is highly influenced by the presence of treatments like anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

“…Anti-RBD Ab could be detected in 72 patients (82%) but only 52 had Ab titers > 4160 AU/mL, a threshold defined as a surrogate of protection by the authors based on a prior study showing a good correlation between this threshold and virus neutralization in vitro (116). (118).…”

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19

“…Many studies that evaluate the quality of the immune response against COVID-19 vaccines in individuals with OHD have been published lately. However, these studies mostly describe the humoral response, with low characterization of the cellular immune responses, which are usually limited to the evaluation of T-cell reactivity through cytokines quantification after antigen stimulation [ 28 , 29 , 30 ], whereas the information regarding functional cellular cytotoxicity is limited to small series of patients for a single disease [ 41 ].This T-cell reactivity achieved 86% rate in individuals with myeloproliferative neoplasms (MPN) after a single dose [ 28 ] and 87.3% and 83% in MM and CLL, respectively [ 30 ] after two doses, whereas the response was widely estimated to be 19–73% in patients with Allo-HSCT [ 30 , 42 ]. These results indicate that the cellular immune response in individuals with OHD might be underestimated due to the poor seroconversion obtained after vaccination.…”

“…However, most of these studies have focused exclusively on the humoral response, with scarce evidence integrating both cellular and humoral responses, which is known to be essential to control COVID-19 infection and avoid the progression to a more severe disease [ 26 , 27 ]. Recently, a few studies have provided data on the cellular response elicited by immunocompromised patients, with rates varying between 45 and 80% [ 28 , 29 , 30 ], which demonstrates that the cellular response does not always correlate with seroconversion as patients may present T-cell responses in the absence of antibodies against SARS-CoV-2 in plasma. However, these results only derive from the release of pro-inflammatory cytokines such as IFN©, TNFα or IL-2, after stimulation with COVID-19 antigens, without providing complete information about the capacity to generate an effective direct cytotoxic response or the antibody-dependent cytotoxicity against SARS-CoV-2-infected cells.…”

Three-dose mRNA-1273 vaccination schedule: sufficient antibody response in majority of immunocompromised hematology patients

“…This does not preclude the generation of potent T cell responses, as was demonstrated recently in patients with rheumatologic or hematologic conditions. [38][39][40] As T cell responses have been demonstrated to protect B cell depleted hematology patients against severe COVID-19, 41 boosting T cell responses with a 3 rd vaccination may, by inference, further harness patients against severe COVID-19. This, however, remains to be confirmed.…”