Project description:Healthcare workers (HCWs) are a high-risk group for hepatitis B virus (HBV) infection. Notably, about 5–10% of the general population does not respond to the HBV vaccination. In this study, we aimed to investigate DNA methylation (DNAm) in order to estimate the biological age of B cells from HCW of both sexes, either responder (R) or non-responder (NR), to HBV vaccination. We used genome-wide DNA methylation data to calculate a set of biomarkers in B cells collected from 41 Rs and 30 NRs between 22 and 62 years old. Unresponsiveness to HBV vaccination was associated with accelerated epigenetic aging (DNAmAge, AltumAge, DunedinPoAm) and was accompanied by epigenetic drift. Female non-responders had higher estimates of telomere length and lower CRP inflammation risk score when compared to responders. Overall, epigenetic differences between responders and non-responders were more evident in females than males. In this study we demonstrated that several methylation DNAm-based clocks and biomarkers are associated with an increased risk of non-response to HBV vaccination, particularly in females. Based on these results, we propose that accelerated epigenetic age could contribute to vaccine unresponsiveness. These insights may help improve the evaluation of the effectiveness of vaccination strategies, especially among HCWs and vulnerable patients.
Project description:Sibling care is a hallmark of the social insects, but its evolution remains challenging to explain. The hypothesis that sibling care evolved from ancestral maternal care in the primitively eusocial insects has been elaborated to involve heterochronic changes in gene expression. This elaboration leads to the prediction that workers in these species will show patterns of gene expression more similar to foundress queens, who express maternal care behavior, than to established queens engaged solely in reproductive behavior. We tested this idea in the bumblebee Bombus terrestris using a microarray platform with ca. 4,500 genes. Unlike in the wasp Polistes metricus, in which support for the above prediction has been obtained, we found that patterns of brain gene expression in foundress and queen bumblebees were more similar to each other than to workers. However, comparisons of lists of differentially expressed genes derived from this study and gene lists from microarray studies in Polistes and the honeybee Apis mellifera suggest that there is a shared set of genes involved in the regulation of related social behaviors across independent eusocial lineages. Together, these results suggest that the multiple independent evolutions of eusociality in the insects involved a combination of shared and different mechanisms.
Project description:Twenty five infants received HBV vaccination and were classified as good or poor responders according to their responses, the number being 12 and 13 respectively. PBMC cells were extracted and epigenome-wide DNA methylation levels were measureed using Illumina Infinium 450K HumanMethylation beadchips. Bisulphite converted DNA from the 25 samples were hybridised to the Illumina Infinium 450K Human Methylation Beadchip v1.2
Project description:The presentation of virus-derived peptides by HLA class I molecules on the surface of an infected cell and the recognition of these HLA-peptide complexes by, and subsequent activation of, CD8+ cytotoxic T cells provides an important mechanism for immune protection against viruses. Recent advances in proteogenomics have allowed researchers to discover a growing number of unique HLA-restricted viral peptides, resulting in a rapidly expanding repertoire of targets for immunotherapeutics (i.e. bispecific antibodies, engineered T-cell receptors (TCRs), chimeric antigen receptor T-cells (CAR-Ts)) to infected tissues. However, genomic variability between viral strains, such as Hepatitis-B virus (HBV), in combination with differences in patient HLA alleles, make it difficult to develop therapeutics against these targets. To address this challenge, we developed a novel proteogenomics approach for generating patient-specific databases that enable the identification of viral peptides based on the viral transcriptomes sequenced from individual patient liver samples. We also utilized DNA sequencing of patient samples to identify HLA genotypes and assist in target selection. Liver samples from 48 HBV infected patients, primarily from Asia, were examined to reconstruct patient-specific HBV genomes, identify regions within the human chromosomes targeted by HBV integrations and obtain a comprehensive view of HBV peptide epitopes using our HLA class-I (HLA-I) immunopeptidomics discovery platform. Two previously reported HLA associated HBV-derived peptides, HLA-A02 binder FLLTRILTI (S194-202) from the large surface antigen and HLA-A11 binder STLPETTVVRR (C141-151) from the capsid protein were validated by our discovery platform, but both were detected at a very low frequencies. In addition, we identified and validated, using heavy peptide analogues, novel strain-specific HBV-HLA associated peptides, such as GSLPQEHIVQK (P606-616) and variants. Overall, our novel approach can guide the development of bispecific antibody, TCR-T, or CAR-T based therapeutics for the treatment of HBV-related HCC and inform vaccine development.
Project description:Twenty five infants received HBV vaccination and were classified as good or poor responders according to their responses, the number being 12 and 13 respectively. PBMC cells were extracted and epigenome-wide DNA methylation levels were measureed using Illumina Infinium 450K HumanMethylation beadchips.
Project description:BackgroundHepatitis B virus (HBV) infection is a world health problem with an estimated 257 million chronically infected people. Indonesia, with 7.1% prevalence of hepatitis B surface antigen (HBsAg), is classified as a moderately endemic country. Healthcare workers (HCWs) are at high occupational risk for HBV infection and potentially becoming transmitters for further infections. In Indonesia, the extent of hepatitis B among HCWs and specific control strategy are not available. This study evaluated the seroprevalence of HBV infection and associated risk factors in HCWs from four areas in South Sulawesi, Indonesia.MethodsA total of 467 HCWs (median age 28 years, male/female 89/378) were recruited. All HCWs were classified into three age groups (< 20-29, 30-39, and ≥ 40 years old), three work types (administration, non-intervention, and intervention), and three service periods (< 5, 5-9, and ≥ 10 years). Data on socio-demographic characteristics and risk factors were obtained by questionnaire and serum samples were tested for HBV markers (HBsAg, its antibody [anti-HBs], and antibody to core antigen [anti-HBc]. Chi-square or Fisher's exact test was used to determine differences in categorical variables, while risk factors were reported as odds ratios (OR).ResultsThe prevalence of current HBV infection (HBsAg+), exposure to HBV (anti-HBc+), and immunity to HBV (anti-HBs+) was 6.2, 19.2, and 26.1%, respectively. Two thirds (66.17%) of all HCWs did not express any of HBV markers. In relation to the age groups, intervention work-type, and service period of HCWs, increasing trends were observed in the exposure to HBV (p < 0.001, p < 0.001, and p < 0.010, respectively) and the immunity to HBV by natural infection (HBsAg-, anti-HBc+, anti-HBs+) (p = 0.004, p < 0.001, and p < 0.010, respectively). Needlestick injury contributed the highest risk factor (OR = 1.71; 95% CI: 1.05-2.77; p = 0.029) for infection acquisition, which mostly occurred in the intervention group (p = 0.046).ConclusionExposure to HBV showed significant association with HCWs' age, work type, and service period. Needlestick injury was the highest risk factor for the acquisition of HBV, with highest events in the intervention work-type. Two thirds of HCWs were still susceptible to HBV infection. Intervention strategies at the national level are required to mount prevention, control, and management of HBV infection in HCWs.
Project description:We used peripheral blood mononuclear cells to study the gene expression profiles of radiation-exposed workers versus control subjects. Human PBMC were isolated from 56 healthy donors who were working in a local Hospital (Bologna, Italy): 28 individuals were x and g radiation-exposed workers, recruited from the Nuclear Medicine and Cardiovascular Units, while the control group consisted of 28 unexposed subjects, working at the same health care facility, matched for sex, age and smoking habits. The mean dosimeter reading, expressed as accumulated doses, during the entire time of employment (range: 1-32 years), was 19.49±37.59 mSv (mean ± SD). All procedures related to the collection of blood samples were performed with an informed consent and according to the protocol approved by the Institutional Review Board.
Project description:Mechanisms of poor responses to vaccines remain unknown. Hepatitis B virus-naïve elderly subjects received three vaccines, including a vaccine against hepatitis B virus (HBV). Pre-vaccination high dimensional analyses of blood using transcriptional profiling and flow cytometry revealed that subjects having increased memory B cell frequencies and higher expression of genes downstream of B cell receptor signaling responded more strongly to the HBV vaccine whereas subjects having higher expression of inflammatory related genes and greater numbers of activated innate immune cells showed a weaker response to this vaccine. The heme-induced response was associated with the poor response to the hepatitis B vaccine. Transcriptional profiling and flow cytometry results were validated in a distinct set of elderly subjects with accuracy greater than 60%. Our study is the first that identifies baseline predictors of responses to vaccines in a population of subjects known to be highly susceptible to infections.
Project description:Apis mellifera workers in temperate climates display two castes; short lived summer bees that engage in nursing, hive maintenance and foraging, and long lived winter bees (diutinus bees) which remain within the hive and are essential for thermoregulation. Label free quantitative proteomic analysis was conducted on A. mellifera workers sampled from July to October 2019 to compare the proteomes of workers as the colony progresses through the year. Proteomic analysis revealed a shift in protein expression in workers in September and October in comparison to July and August samples. Workers samples in September and October had a higher abundance of proteins associated with oxidative phosphorylation and storage proteins such as hexamerin. Interestingly, a shift in protein expression was detected in newly emerged bees between July to October, providing evidence that workers have adapted to emerge with a different protein profile in preparation for the winter months.