Virus Chimp162
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Project description:Next-generation T-cell-directed vaccines for COVID-19 aim to induce durable T-cell immunity against circulating and future hypermutated SARS-CoV-2 variants. Mass Spectrometry (MS)based immunopeptidomics holds promise for guiding vaccine design, but computational challenges impede the precise and unbiased identification of conserved T-cell epitopes crucial for vaccines against rapidly mutating viruses. We introduce a computational framework and analysis platform integrating a novel machine learning algorithm, immunopeptidomics, intra-host data, epitope immunogenicity, and geo-temporal CD8+ T-cell epitope conservation analyses. Central to our approach is MHCvalidator, a novel artificial neural network algorithm enhancing MS-based immunopeptidomics sensitivity by modeling antigen presentation and sequence features. MHCvalidator identified a novel nonconventional SARS-CoV-2 T-cell epitope presented by B7 supertype molecules, originating from a +1-frameshift in a truncated Spike (S) antigen, supported by ribo-seq data. Intra-host analysis of SARS-CoV-2 proteomes from ~100,000 COVID-19 patients revealed a prevalent S antigen truncation in ~51% of cases, exposing a rich source of frameshifted viral antigens. Our framework includes EpiTrack, a new computational pipeline tracking global mutational dynamics of MHCvalidator-identified SARS-CoV-2 CD8+ epitopes from vaccine BNT162b4. While most vaccine-encoded CD8+ epitopes exhibit global conservation from January 2020 to October 2023, a highly immunodominant A*01-associated epitope, especially in hospitalized patients, undergoes substantial mutations in Delta and Omicron variants. Our approach unveils unprecedented SARS-CoV-2 T-cell epitopes, elucidates novel antigenic features, and underscores mutational dynamics of vaccine-relevant epitopes. The analysis platform is applicable to any viruses, and underscores the need for continual vigilance in T-cell vaccine development against the evolving landscape of hypermutating SARS-CoV-2 variants.
2024-10-14 | PXD052187 | Pride
Project description:The identification of protective epitopes in bacterial pathogens using mass spectrometry proteomics is essential for advancing vaccine design, especially against the backdrop of increasing antibiotic resistance. Our study introduces an innovative strategy, leveraging multi-modal mass spectrometry techniques, to decode the interaction between a neutralizing monoclonal antibody (nAb) and the Streptolysin O (SLO) toxin from Streptococcus pyogenes. By integrating XL-MS, HDX-MS, and computational modeling, we successfully identified and characterized a conserved protective epitope within SLO, providing critical insights for vaccine development. Utilizing a novel nAb sequenced through de novo bottom-up shotgun MS, we explored its binding mechanism and interaction with the SLO antigen with structural proteomics such as XL-MS and HDX-MS. This study not only clarifies the conformational epitope structure but also illuminated the antibody's unique protective mechanism mode. The epitope's high conservation (near 100%) across various S. pyogenes strains underscores its potential as a universal target for vaccine strategies. Additionally, our approach overcomes traditional limitations in epitope mapping, showcasing the power of mass spectrometry in resolving challenging antibody-antigen interfaces. Our findings represent a significant leap in understanding bacterial pathogenesis and immune defense, laying the groundwork for designing next-generation vaccines. The data generated from this study can guide the development of targeted therapies and vaccines, offering new solutions to combat severe streptococcal infections.
2024-05-06 | PXD047461 | Pride
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). Transcriptomic profilling of blood collected pre-vaccination and post-vaccination was performed in order to identify candidate biomarkers of antibody response to the different vaccines.
2020-05-19 | GSE125860 | GEO
Project description:A human embryonic fibroblast cell line was synchronously infected with poliovirus in the absence or presence of interferon-α, or with vacciniavirus, a virus that is not inhibited by interferon. The titers were sufficient to yield productive infection in a majority of the cells. The cells were harvested in triplicate at various time-points, and the transcriptosome compared with mock infected cells using oligo-based 35 k microarrays. The project had two purposes: to characterize the cellular response and to look for candidate genes involved in viral defense. The changes in gene expression due to vaccinia virus did not correspond to those caused by poliovirus. More surprisingly, neither did the changes when comparing 8 h and 16 h of poliovirus infection. However, a large proportion of the genes up-regulated by interferon-α were also up-regulated by poliovirus, both at 8 h and 16 h. Interferon-α inhibited poliovirus replication, thus the observations suggest that the cells do launch an antiviral response to poliovirus. Moreover, as interferon genes were not induced, the data indicate that several of the relevant genes can be activated in an interferon independent manner. Further analyses of the data led to a list of candidate antiviral genes. Functional information was limited, or absent, for most of these genes. Keywords: Poliovirus; Vacciniavirus; Interferon; Microarray; Gene expression; Defense genes
2006-10-16 | GSE5549 | GEO
Project description:Epstein-Barr virus (EBV) ubiquitously infects global population and leads to a variety malignancies and autoimmune diseases. It establishes its lytic-latency life cycle relying on the tropism transition between B cell and epithelial cell, during which its critical glycoprotein gB and gHgL act as the fusion apparatus mediating viral recognition and membrane fusion in either cell type. Thus. simultaneous targeting to fusion apparatus would be ideal strategy to construct potent EBV prophylactic vaccine. In this study, we designed chimeric nanoparticle multivalently displaying gB and gHgL with even gp42 upon the nanoparticle surface, inducing significantly robust neutralizing antibody generation in both murine and non-human primate models. As we further identify the comparable immunization potency between chimeric nanoparticle and whole live virion and preponderance of gB in neutralizing antibody elicitation, we used single-B cell sequencing to dissect the B cell response to chimeric nanoparticle immunization in mouse and isolate a gB-specific neutralizing antibody Fab5 targeting novel vulnerable site. These findings offers insight to advanced vaccine design for EBV and other herpesviruses.
2025-01-01 | GSE245792 | GEO
Project description:We advanced a promising experimental vaccine for immunizing against the Lassa virus surface glycoprotein as a candidate for human trials. Preclinical evaluation of the vaccine candidate based on a live vesicular stomatitis virus (VSV) vector showed that it was highly efficacious in cynomolgus macaques consistent with earlier research studies, and that the animals developed serum antibodies that could mediate antiviral effector functions including direct neutralization of virus infectivity. As part of this evaluation, we analyzed whole-blood transcriptomes from each study subject prior to vaccination and at 1 day and 3 days post-vaccination.
2024-11-30 | GSE246148 | GEO
Project description:Pre-existing immunity impacts vaccine responses to endemic respiratory viruses such as influenza, but directly connecting influenza infections early in life with immune responses decades later is difficult. However, H2N2 stopped circulating in the human population in 1968, creating the opportunity to directly evaluate the impact of early H2N2 exposure on vaccine responses 50 years later. Here, we vaccinate individuals born before (H2 Exposed) or after (H2 Naïve) 1968 with an H2 HA DNA plasmid and/or a ferritin nanoparticle vaccine. H2 Exposed individuals generated a rapid B cell recall response that differed in potency, cross-reactivity, immunoglobulin repertoire, epitope targeting and phenotype from the de novo response in H2 Naïve individuals. Furthermore, vaccinating with a DNA versus a protein nanoparticle vaccine altered the response in H2 Naïve but not H2 Exposed individuals. This study clearly establishes and describes the life-long impact of influenza HA-specific memory B cells formed early in life on vaccine responses decades later.
2025-02-28 | GSE283403 | GEO
Project description:Laboratory strain poliovirus was hybridized to the array as a control run and a proof of concept. Degree of cross hybridization between polio nucleic acid and non-polio probes was evaluated. Specificity of the probe design was determined. Keywords: control study: target detection and specificity
2008-02-28 | GSE10566 | GEO
Project description:Vaccine development involves time-consuming and expensive evaluation of candidate vaccines in animal models. As mediators of both innate and adaptive immune responses dendritic cells (DCs) are considered to be highly important for vaccine performance. Here we evaluated in how far the response of DCs to a vaccine in vitro is in line with the immune response the vaccine evokes in vivo. To this end, we investigated the response of murine bone marrow-derived DCs to whole inactivated virus (WIV) and subunit (SU) influenza vaccine preparations. These vaccine preparations were chosen because they differ in the immune response they evoke in mice with WIV being superior to SU vaccine through induction of higher virus-neutralizing antibody titers and a more favorable Th1-skewed response phenotype. To evaluate if in vivo immunogenicity is reflected by DC reactions in vitro we studied the gene expression signature of murine bone-marrow-derived conventional DCs (cDCs) upon stimulation with WIV or SU influenza vaccine or, for reasons of comparison, with live influenza virus. Dendritic cells stimulated with PBS served as a control. Gene expression analysis was performed on samples 4, 12 and 24 hours after the start of stimulation.
2015-02-13 | E-MTAB-3115 | biostudies-arrayexpress