HDAC Inhibitors as Epigenetic Regulators

Serum neutralizing activity was present in all the HCWs tested and in only a minority of the fingolimod-treated patients (16.6%). in Rabbit Polyclonal to TK (phospho-Ser13) patients treated with ocrelizumab (< 0.0001), fingolimod (< 0.0001), and cladribine (= 0.010) compared to HCWs and IFN-Ctreated patients. Serum neutralizing activity was present in all the HCWs tested and in only a minority of the fingolimod-treated patients (16.6%). T-cellCspecific response was detected in the majority of patients with MS (62%), albeit with significantly lower IFN- levels compared to HCWs. The lowest frequency of T-cell response was found Menaquinone-4 in fingolimod-treated patients (14.3%). T-cellCspecific response correlated with lymphocyte count and anti-RBD antibody titer ( = 0.554, < 0.0001 and = 0.255, = 0.0078 respectively). IFN- T-cell response was mediated by both CD4+ and CD8+ T cells. Conversation mRNA vaccines induce both Menaquinone-4 humoral and cell-mediated specific immune responses against spike peptides in all HCWs and in the majority of patients with MS. Menaquinone-4 These results carry relevant implications for managing vaccinations, suggesting promoting vaccination in all treated patients with MS. Classification of Evidence This study provides Class III data that SARS-CoV-2 mRNA vaccination induces both humoral and cell-mediated specific immune responses against viral spike proteins in a majority of patients with MS. Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS and is a leading cause of disability in young adults1 in Western countries. Most people with MS are treated with immunomodulatory or immunosuppressive medications, which might increase the risk of opportunistic infections, infection-related hospitalization, and infection-related mortality rates.2-4 The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a human-to-human transmissible disease with a severe global health impact5 and hard clinical management.6,7 Large-scale vaccination is the single most effective general public health measure for controlling the COVID-19 pandemic and a global effort to develop and distribute an effective vaccine produced several effective options. Several data are now available about the efficacy of the mRNA platform vaccines, namely BNT162b2 and mRNA-1273 vaccines, in inducing strong antibody and cell-mediated immune responses in naive healthy individuals.8-12 The ability of vaccines to induce a coordinated induction of both humoral- and cell-mediated arms is fundamental for a more effective fighting of SARS-CoV-2 contamination13,14; this is particularly crucial in people with MS treated with immunotherapy targeting pathogenetic inflammatory processes.15,16 Disease-modifying treatments (DMTs) used in MS act at different levels of the immune system. Based on their mechanism of action, they can be divided into: (1) immunomodulators: interferon (IFN)C, glatiramer Menaquinone-4 acetate, dimethyl fumarate, and teriflunomide; (2) cell trafficking alteration molecules like S1P receptor modulators (i.e., fingolimod) and 4-integrin antibody (natalizumab); (3) depletive drugs (ocrelizumab, an anti-CD20 antibody; cladribine, a purine analog that interferes with DNA synthesis inducing a prolonged lymphocyte depletion; and alemtuzumab, an anti-CD52 antibody). The overall effects of these DMTs in affecting the humoral and cell-mediated immune responses to SARS-CoV-2 vaccine is usually unknown. Preliminary data have been published suggesting that this antibody response to BNT162b2 vaccine is usually impaired in people with MS treated with fingolimod and ocrelizumab, whereas it is preserved in those treated with cladribine.17-19 More recently, Guerrieri et al.20 in a real-word study on 32 people with MS have shown a higher frequency of the humoral response (62.5%) in patients treated with fingolimod. These data are essential for health decision and need to be confirmed and supplemented by the evaluation of the T-cellCspecific response. The aim of this study was to evaluate the antiCregion-binding domain name (RBD) neutralizing antibodies and spike (S)-specific T-cell response after the full SARS-CoV-2 vaccination of patients with MS treated with different DMTs. Methods Standard Protocol Approvals, Registrations, and Patient Consents Human study protocols were approved by the Lazzaro Spallanzani National Institute for Infectious Diseases (INMI) Ethical Committee (approvals 297/2021 and 319/2021). The study protocols followed the ethics principles for human experimentation in agreement with the Declaration of Helsinki. Written informed consent was obtained from all participants. Study Population Participants were enrolled from 2 parallel prospective studies conducted at the INMI Lazzaro Spallanzani. In detail, the studies evaluated the immune response to SARS-CoV-2 vaccination in both health care workers (HCWs) enrolled at Menaquinone-4 INMI and in patients.