Immunogenicity and Tolerance of BNT162b2 mRNA Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (ASCT) induces acquired immunodeficiency, potentially altering vaccine response. Herein, we aimed to explore the clinical tolerance and the humoral and cellular immune responses following anti-SARS-CoV-2 vaccination in ASCT recipients. METHODS: A prospective, non-randomized, controlled study that involved 43 ASCT subjects and 31 healthy controls. Humoral response was investigated using the Elecsys® test anti-SARS-CoV-2. Cellular response was assessed using the QFN® SARS-CoV-2 test. The lymphocyte cytokine profile was tested using the LEGENDplex™ HU Th Cytokine Panel Kit (12-plex). RESULTS: Adverse effects (AE) were observed in 69% of patients, encompassing pain at the injection site, fever, asthenia, or headaches. Controls presented more side effects like pain in the injection site and asthenia with no difference in the overall AE frequency. Both groups exhibited robust humoral and cellular responses. Only the vaccine transplant delay impacted the humoral response alongside a previous SARS-CoV-2 infection. Noteworthily, controls displayed a Th1 cytokine profile, while patients showed a mixed Th1/Th2 profile. CONCLUSIONS: Pfizer-BioNTech® anti-SARS-CoV-2 vaccination is well tolerated in ASCT patients, inducing robust humoral and cellular responses. Further exploration is warranted to understand the impact of a mixed cytokine profile in ASCT patients.

Immunogenicity of Mix-and-Match CoronaVac/BNT162b2 Regimen versus Homologous CoronaVac/CoronaVac Vaccination: A Single-Blinded, Randomized, Parallel Group Superiority Trial.

(1) Background: This study aimed to compare the immunogenicity of the mix-and-match CoronaVac/BNT162b2 vaccination to the homologous CoronaVac/CoronaVac regimen. (2) Methods: We conducted a simple-blinded randomized superiority trial to measure SARS-CoV-2 neutralization antibodies and anti-spike receptor binding domain (RBD) IgG concentrations in blood samples of participants who had received the first dose of CoronaVac vaccine followed by a dose of BNT162b2 or CoronaVac vaccine. The primary endpoint for immunogenicity was the serum-neutralizing antibody level with a percentage of inhibition at 90% at 21-35 days after the boost. A difference of 25% between groups was considered clinically relevant. (3) Results: Among the 240 eligible participants, the primary endpoint data were available for 100 participants randomly allocated to the mix-and-match group versus 99 participants randomly allocated to the homologous dose group. The mix-and-match regimen elicited significantly higher levels of neutralizing antibodies (median level of 96%, interquartile range (IQR) (95-97) versus median level of 94%, IQR (81-96) and anti-spike IgG antibodies (median level of 13,460, IQR (2557-29,930) versus median level of 1190, IQR (347-4964) compared to the homologous group. Accordingly, the percentage of subjects with a percentage of neutralizing antibodies > 90% was significantly higher in the mix-and-match group (90.0%) versus the homologous (60.6%). Interestingly, no severe events were reported within 30 days after the second dose of vaccination in both groups. (4) Conclusions: Our data showed the superiority of the mix-and-match CoronaVac/BNT162b2 vaccination compared to the CoronaVac/CoronaVac regimen in terms of immunogenicity, thus constituting a proof-of-concept study supporting the use of inactivated vaccines in a mix-and-match strategy while ensuring good immunogenicity and safety.

Increased Interleukin-17 and decreased BAFF serum levels in drug-free acute schizophrenia.

Hypotheses regarding an immune-cytokine basis of schizophrenia have been postulated with controversial findings and a lack of data related to many cytokines. The aim of this study was to assess serum levels of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Transforming Growth Factor-ß (TGF-ß), Interleukin-17 (IL-17) and B-cell Activating Factor (BAFF) in schizophrenic patients and to determine correlations between cytokine levels and clinical parameters. Serum cytokine levels were measured with ELISA techniques in 60 neuroleptic-free patients on acute phase of the disease (BPRS≥40) and 28 healthy controls matched for age and sex. Current symptoms were assessed with Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). No significant difference was found between patients and controls regarding IFN-γ serum levels. IL-4 was not detected in both groups. Patients exhibited significantly higher IL-17 and lower BAFF serum levels. IL-17 and BAFF levels were negatively correlated in schizophrenic patients. SANS global score was negatively correlated with IL-17 and positively correlated with IFN-γ serum levels. These results argue against the involvement of Th1 or Th2 population cells in schizophrenia. IL-17 and BAFF could be valuable markers for schizophrenia.

High prevalence of Human Herpesvirus 8 in schizophrenic patients.

Many studies have reported an association between Herpes family viruses and an increased risk of schizophrenia, but the role of Human Herpesvirus 8 (HHV8) has never been investigated. This study aimed to assess HHV8 prevalence in schizophrenic patients as well as the possible association between HHV8 infection and schizophrenia clinical features. We consecutively enrolled 108 patients meeting fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria of schizophrenia and 108 age and sex matched controls. Data about a number of demographic characteristics and potential HHV8 risk factors of infection were collected. Standardized psychopathology measures, disease severity and functioning level were obtained using Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Clinical Global Impressions (CGI) and Global Assessment of functioning (GAF). The presence of anti-HHV8 antibodies was analyzed using an indirect immunofluorescence assay. A higher prevalence of HHV8 infection in schizophrenic patients than in controls was found. Marital status, having children, sexual behavior and risk factors of blood transmission were not associated with HHV8 prevalence. However, among schizophrenic patients, HHV8 prevalence was statically associated with positive symptoms. To our knowledge, this would be the first report of a possible role of HHV8 in the pathogenesis of schizophrenia. To prove this hypothesis, further investigation of HHV8 in schizophrenia with larger samples is needed.

A novel insight on chronic AlCl3 neurotoxicity through IL-6 and GFAP expressions: modulating effect of functional food fenugreek seeds.

OBJECTIVE: This study was designed to review the effect of chronic aluminium exposure on interleukin-6 (IL-6) secretion in the posterior brain and test the putative modulating effect of fenugreek seeds. METHODS: Female Wistar rats were divided into four groups: control; AlCl3 during 5 months (500 mg/kg body weight, intragastric for 1 month then 1600 ppm via the drinking water); AlCl3 plus fenugreek seed powder (FSP) (5%) during the last 2 months and FSP alone. RESULTS: Oral administration of aluminium chloride during 5 months caused hypoproduction of IL-6 together with a decrease in GFAP reactivity and an alteration of antioxidant status in the posterior brain. On the other hand, fenugreek seeds supplementation was able to enhance IL-6 expression, re-increase GFAP reactivity, and modulate the pro-oxidant-related effect. DISCUSSION: In the context of recent researches, IL-6 hypoproduction in the posterior brain could be a novel mechanism of Al chronic toxicity with a direct effect on glial cells. Using FSP as a diet supplement could offer a neuroprotective effect against Al toxicity. This could be mediated by astroglial cells protection, antioxidant and immunomodulatory actions.