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Immune biomarkers to predict SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies.

ABSTRACT: There is evidence of reduced SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies. We hypothesized that tumor and treatment-related immunosuppression can be depicted in peripheral blood, and that immune profiling prior to vaccination can help predict immunogenicity. We performed a comprehensive immunological characterization of 83 hematological patients before vaccination and measured IgM, IgG, and IgA antibody response to four viral antigens at day +7 after second-dose COVID-19 vaccination using multidimensional and computational flow cytometry. Health care practitioners of similar age were the control group (n = 102). Forty-four out of 59 immune cell types were significantly altered in patients; those with monoclonal gammopathies showed greater immunosuppression than patients with B-cell disorders and Hodgkin lymphoma. Immune dysregulation emerged before treatment, peaked while on-therapy, and did not return to normalcy after stopping treatment. We identified an immunotype that was significantly associated with poor antibody response and uncovered that the frequency of neutrophils, classical monocytes, CD4, and CD8 effector memory CD127low T cells, as well as naive CD21+ and IgM+D+ memory B cells, were independently associated with immunogenicity. Thus, we provide novel immune biomarkers to predict COVID-19 vaccine effectiveness in hematological patients, which are complementary to treatment-related factors and may help tailoring possible vaccine boosters.

SUBMITTER: Tamariz-Amador LE

PROVIDER: S-EPMC8669666 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFew data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients.ObjectiveTo investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy.MethodsWe measured SARS-CoV-2 anti-spike antibodies, anti-Omicron neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80-92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti-Omicron). T cell response was assessed at T post-3D.ResultsAn increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the Omicron variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti-Omicron neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the Omicron variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts.ConclusionFHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response.

Project description:BackgroundCancer patients particularly those with hematological malignancies are at higher risk of affecting by severe coronavirus disease 2019 (COVID-19). Due to the immunocompromised nature of the disease and the immunosuppressive treatments, they are more likely to develop less antibody protection; therefore, we aimed to evaluate the immunogenicity of COVID-19 vaccines in patients with hematological malignancies.MethodsA comprehensive systematic search was conducted in PubMed, Scopus, and Web of Science databases, as well as Google scholar search engine as of December 10, 2021. Our primary outcomes of interest comprised of estimating the antibody seropositive rate following COVID-19 vaccination in patients with hematological malignancies and to compare it with those who were affected by solid tumors or healthy subjects. The secondary outcomes were to assess the vaccine's immunogenicity based on different treatments, status of the disease, and type of vaccine. After the two-step screening, the data were extracted and the summary measures were calculated using a random-effect model.ResultsA total of 82 articles recording 13,804 patients with a diagnosis of malignancy were included in the present review. The seropositive rates in patients with hematological malignancies after first and second vaccine doses were 30.0% (95% confidence interval (95%CI): 11.9-52.0) and 62.3% (95%CI 56.0-68.5), respectively. These patients were less likely to develop antibody response as compared to cases with solid tumors (RR 0.73, 95%CI 0.67-0.79) and healthy subjects (RR 0.62, 95%CI 0.54-0.71) following complete immunization. Chronic lymphocytic leukemia (CLL) patients had the lowest response rate among all subtypes of hematological malignancies (first dose: 22.0%, 95%CI 13.5-31.8 and second dose: 47.8%, 95%CI 41.2-54.4). Besides, anti-CD20 therapies (5.7%, 95%CI 2.0-10.6) and bruton's tyrosine kinase inhibitors (26.8%, 95%CI 16.9-37.8) represented the lowest seropositiveness post first and second doses, respectively. Notably, patients who were in active status of disease showed lower antibody detection rate compared to those on remission status (RR 0.87, 95%CI 0.76-0.99). Furthermore, lower rate of seropositivity was found in patients received BNT162.b2 compared to ones who received mRNA-1273 (RR 0.89, 95%CI 0.79-0.99).ConclusionOur findings highlight the substantially low rate of seroprotection in patients with hematological malignancies with a wide range of rates among disease subgroups and different treatments; further highlighting the fact that booster doses might be acquired for these patients to improve immunity against SARS-CoV-2.

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Immune biomarkers to predict SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies.

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