Safety and Immunogenicity of Mix-Match of Vaccines -Covishield and Covaxin – a Pilot Study

This single-center prospective observational study was conducted to assess the safety and immunogenicity of combination vaccines AstraZeneca’s ChAdOx1-nCov-19 (Covishield in India) and inactivated whole virion BBV152 (Covaxin). A total of 330 unvaccinated healthy volunteers were screened for SARS-COV2 seropositivity. RT PCR tests were conducted for seronegative volunteers (n =44). They were randomly assigned to four groups and given either same or mixed vaccines at an interval of 4 weeks between the two doses. Mix and match of vaccines did not evoke any adverse events. Combination of vaccines elicited similar immune responses in 4 groups. They were further studied dividing into homologous and heterologous vaccine groups. In Conclusion, Combination vaccines are safe and immunogenic and heterologous vaccines elicit better immunogenic response.

Predictors of an Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab: A Multicenter Study

BackgroundTreatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX).MethodsWe analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls immunized with BNT162b2 mRNA vaccine participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG measured at 2 to 6 weeks after the second vaccine dose. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX patients (n=48) immunized with the BNT162b2 mRNA vaccine.Results AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from non-responders by lower number of RTX courses (median (range) 3 (1-10) vs 5 (1-15), p=0.007; lower cumulative RTX dose 6943.11±5975.74 vs 9780.95±7240.12 mg, p=0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78±576.28 vs. 884.33±302.31 mg/dL, p=0.002, and extended interval between RTX treatment and vaccination, 469.82±570.39 vs 162.08±160.12 days, p=0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046-0.96, p=0.044 and OR 0.189, 95% CI 0.036-0.987, p=0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, 63.3% positive and 88.9% negative predictive values.ConclusionsThe predicting calculator might guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.

In Silico Taste, Cytochrome and Toxicity Prediction Study of Major Chamomile Constituents

Chamomile is an ancient herb used for various medications. It contains many bioactive constituents such as volatile oils, terpenoids, flavonoids, lactones, acid esters, glycosides and others. By reviewing many references, a confliction appeared of using Chamomile preparations to treat primary teeth eruption symptoms as a therapy administered by pediatric dentist or pediatrician. In this study, thirteen bioactive constituents (α-bisabolol (B), chamazulene (C), umbelliferone (U), apigenin (A), apigetrin (AT), apiin (AI), luteolin (L), quercetin (Q), quercimertrin (QT), rutin (R), α-cadinene (CD), α-farnesene (F), and matricarin (M) were subject to computational predication through various online websites to predicate their taste, activity towards several CYP450 enzymes and their action as Hepatotoxic, carcinogenic, immunotoxic, mutagenic, and cytotoxic compounds. Our calculations revealed several points such as high value of taste predication indicated that Chamomile constituents under study were with sour taste, did not classify as individual fatal compound Class (GHS) 1 or 2, 44.87% of them showed inhibition character toward specific cytochrome P450 enzyme while 43.59% were non- inhibition character, more than (0.5) probability predication of various cytochrome P450 enzymes gave a positive activity that may affect liver functions. Also, hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity predictions were more than (0.5), unsaturated Chamomile constituent (Farnesene, F) had highest immune – and mutagenic properties whilst the disaccharide flavonoid (Rutin, R) had the highest Carcino- immunogenic response. According to the above notes, our conclusion is to use minimum concentration of Chamomile preparation for less period of time and lowest repeating intake that ensure effective treatment of teething symptoms under supervision of pediatricians with minimum side effect.

Genipin-Based Crosslinking of Jellyfish Collagen 3D Hydrogels

Collagen-based hydrogels are an attractive option in the field of cartilage regeneration with features of high biocompatibility and low immunogenic response. Crosslinking treatments are often employed to create stable 3D gels that can support and facilitate cell embodiment. In this study, we explored the properties of JellaGel™, a novel jellyfish material extracted from Rhizostoma pulmo. In particular, we analyzed the influence of genipin, a natural crosslinker, on the formation of 3D stable JellaGel™ hydrogels embedding human chondrocytes. Three concentrations of genipin were used for this purpose (1 mM, 2.5 mM, and 5 mM). Morphological, thermal, and mechanical properties were investigated for the crosslinked materials. The metabolic activity of embedded chondrocytes was also evaluated at different time points (3, 7, and 14 days). Non-crosslinked hydrogels resulted in an unstable matrix, while genipin-crosslinked hydrogels resulted in a stable matrix, without significant changes in their properties; their collagen network revealed characteristic dimensions in the order of 20 µm, while their denaturation temperature was 57 °C. After 7 and 14 days of culture, chondrocytes showed a significantly higher metabolic activity within the hydrogels crosslinked with 1 mM genipin, compared to those crosslinked with 5 mM genipin.

Role of lipopolysaccharides in potential applications of nanocarrier systems

Background: Lipopolysaccharides (LPS) are considered the main molecular component in the outer membrane of gram-negative bacteria. The LPS molecule in the bacterial cell wall acts as a primary physical barrier and protects gram-negative bacteria from the surrounding environment. LPS (endotoxins) show immunomodulatory therapeutic properties as well as toxicity to the host cell, whereas potential applications encompass. Objective: This review article aims to describe the recent developments of lipopolysaccharides in nanocarrier systems for various applications such as vaccination, cancer chemotherapy and immune stimulants action. Different nanocarriers like cubosomes, niosomes, dendrimers and metal nanoparticles used in the delivery of actives are employed to decorate lipopolysaccharide molecules superficially. Methods: A narrative review of all the relevant papers known to the author was conducted. Conclusion: Commercially available lipid nanoparticles contribute to many advances as promising nanocarriers in cancer therapy and are used as a vaccine adjuvant by improving the immune response due to their properties such as size, shape, biocompatibility, and biodegradability. Whereas lipopolysaccharide-decorated nanoparticles change the host's tolerability and increase the effectiveness of molecule in cancer immunotherapy. These nanoconjugate systems enhance overall immunogenic response and effectiveness in vaccine immunotherapy and targeted therapy, not only limited to humans application but also for poultry and aquaculture. Newer opportunities using lipopolysaccharides for the treatment and management of diseases with unique characteristics like the presence of lipoprotein that act as an alternative for bacterial infections over conventional dosage forms.

Mutational signature profiling classifies subtypes of clinically different mismatch repair deficient tumors with a differential immunogenic response potential

ABSTRACTBackgroundMismatch repair (MMR) deficiency is the hallmark of tumors from Lynch syndrome (LS), sporadic MLH1 hypermethylated, and Lynch-like syndrome (LLS), but there is a lack of understanding of the variability in their mutational profiles based on clinical phenotypes. The aim of this study was to perform a molecular characterization to identify novel features that can impact tumor behavior and clinical management.MethodsWe tested 105 MMR-deficient colorectal cancer tumors (25 LS, 35 LLS, and 45 sporadic) for global exome microsatellite instability, cancer mutational signatures, mutational spectrum and neoepitope load.Results78% of tumors showed high contribution of MMR-deficient mutational signatures, high level of global exome microsatellite instability, loss of MLH1/PMS2 protein expression and included sporadic tumors. 22% of tumors showed weaker features of MMR deficiency, 73% lost MSH2/MSH6 expression and included half of LS and LLS tumors. Remarkably, 9% of all tumors lacked global exome microsatellite instability. Lastly, HLA-B07:02 could be triggering the neoantigen presentation in tumors that show the strongest contribution of MMR-deficient tumors.ConclusionsNext-generation sequencing approaches allow for a granular molecular characterization of MMR-deficient tumors, which can be essential to properly diagnose and treat patients with these tumors in the setting of personalized medicine.

Comparative quantitative analysis of SARS-CoV-2 Spike neutralizing antibody titers following two anti COVID-19 vaccines in India

In COVID 19 pandemic, first line of defense is effective vaccination program. Because of multiple platforms available for vaccine production we tested relative immunogenicity of two vaccines available in India, Covaxin and Covishield We performed quantitative analysis of neutralizing antibodies to SARS Cov2 spike (receptor binding domain ) protein, from sera of 53 subjects who completed vaccines schedules. There was significantly higher immunogenic response with Covishield as compared to Covaxin and are independent of age. Studies on a large scale with long term follow up are needed to further advance the knowledge in this domain.

Levels of Produced Antibodies after Vaccination with mRNA Vaccine; Effect of Previous Infection with SARS-CoV-2

The aim of this study was to estimate the immunogenic effect of mRNA vaccine against SARS-CoV-2. This study included 510 participants who received mRNA vaccine. The measurement of anti-COVID-19 antibodies was performed using the Abbott SARS-CoV-2 IgG quantitative assay (Abbott). Overall, mean titer of anti-Spike antibodies was 19,319.2 ± 1787.5 AU/mL. Vaccination induced a robust immunogenic response in those previously infected with SARS-CoV-2 compared with non-infected subjects. Additionally, individuals that were asymptomatic after vaccination produced lower levels of antibodies compared to feverish individuals. In conclusion, remarkably high levels of anti-Spike COVID-19 antibodies were observed after vaccination.