ABSTRACT
PURPOSE: The SARS-CoV-2 Omicron variant of concern (VOC) and subvariants like BQ.1.1 demonstrate immune evasive potential. Little is known about the efficacy of booster vaccinations regarding this VOC and subvariants in cancer patients. This study is among the first to provide data on neutralizing antibodies (nAb) against BQ.1.1. METHODS: Cancer patients at our center were prospectively enrolled between 01/2021 and 02/2022. Medical data and blood samples were collected at enrollment and before and after every SARS-CoV-2 vaccination, at 3 and 6 months. RESULTS: We analyzed 408 samples from 148 patients (41% female), mainly with solid tumors (85%) on active therapy (92%; 80% chemotherapy). SARS-CoV-2 IgG and nAb titers decreased over time, however, significantly increased following third vaccination (p < 0.0001). NAb (ND50) against Omicron BA.1 was minimal prior and increased significantly after the third vaccination (p < 0.0001). ND50 titers against BQ.1.1 after the third vaccination were significantly lower than against BA.1 and BA.4/5 (p < 0.0001) and undetectable in half of the patients (48%). Factors associated with impaired immune response were hematologic malignancies, B cell depleting therapy and higher age. Choice of vaccine, sex and treatment with chemo-/immunotherapy did not influence antibody response. Patients with breakthrough infections had significantly lower nAb titers after both 6 months (p < 0.001) and the third vaccination (p = 0.018). CONCLUSION: We present the first data on nAb against BQ.1.1 following the third vaccination in cancer patients. Our results highlight the threat that new emerging SARS-CoV-2 variants pose to cancer patients and support efforts to apply repeated vaccines. Since a considerable number of patients did not display an adequate immune response, continuing to exhibit caution remains reasonable.
ABSTRACT
With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old's working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.
Subject(s)
COVID-19 , Vaccines , Humans , Adult , COVID-19 Vaccines , CD8-Positive T-Lymphocytes , Antibody Formation , Leukocytes, Mononuclear , SARS-CoV-2 , COVID-19/prevention & control , CytokinesABSTRACT
OBJECTIVES: The effect of different modes of immunosuppressive therapy in autoimmune inflammatory rheumatic diseases (AIRDs) remains unclear. We investigated the impact of immunosuppressive therapies on humoral and cellular responses after two-dose vaccination. METHODS: Patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis treated with TNFi, IL-17i (biological disease-modifying antirheumatic drugs, b-DMARDs), Janus-kinase inhibitors (JAKi) (targeted synthetic, ts-DMARD) or methotrexate (MTX) (conventional synthetic DMARD, csDMARD) alone or in combination were included. Almost all patients received mRNA-based vaccine, four patients had a heterologous scheme. Neutralising capacity and levels of IgG against SARS-CoV-2 spike-protein were evaluated together with quantification of activation markers on T-cells and their production of key cytokines 4 weeks after first and second vaccination. RESULTS: 92 patients were included, median age 50 years, 50% female, 33.7% receiving TNFi, 26.1% IL-17i, 26.1% JAKi (all alone or in combination with MTX), 14.1% received MTX only. Although after first vaccination only 37.8% patients presented neutralising antibodies, the majority (94.5%) developed these after the second vaccination. Patients on IL17i developed the highest titres compared with the other modes of action. Co-administration of MTX led to lower, even if not significant, titres compared with b/tsDMARD monotherapy. Neutralising antibodies correlated well with IgG titres against SARS-CoV-2 spike-protein. T-cell immunity revealed similar frequencies of activated T-cells and cytokine profiles across therapies. CONCLUSIONS: Even after insufficient seroconversion for neutralising antibodies and IgG against SARS-CoV-2 spike-protein in patients with AIRDs on different medications, a second vaccination covered almost all patients regardless of DMARDs therapy, with better outcomes in those on IL-17i. However, no difference of bDMARD/tsDMARD or csDMARD therapy was found on the cellular immune response.