Next-generation COVID-19 vaccines: here come the proteins.
Ontology highlight
ABSTRACT:
SUBMITTER: Blakney AK
PROVIDER: S-EPMC7906748 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Next-generation COVID-19 vaccines: here come the proteins.
Blakney Anna K AK McKay Paul F PF
Lancet (London, England) 20210129 10275
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Project description:The world is in need of next-generation COVID-19 vaccines. Although first-generation injectable COVID-19 vaccines continue to be critical tools in controlling the current global health crisis, continuous emergence of SARS-CoV-2 variants of concern has eroded the efficacy of these vaccines, leading to staggering breakthrough infections and posing threats to poor vaccine responders. This is partly because the humoral and T-cell responses generated following intramuscular injection of spike-centric monovalent vaccines are mostly confined to the periphery, failing to either access or be maintained at the portal of infection, the respiratory mucosa (RM). In contrast, respiratory mucosal-delivered vaccine can induce immunity encompassing humoral, cellular, and trained innate immunity positioned at the respiratory mucosa that may act quickly to prevent the establishment of an infection. Viral vectors, especially adenoviruses, represent the most promising platform for RM delivery that can be designed to express both structural and nonstructural antigens of SARS-CoV-2. Boosting RM immunity via the respiratory route using multivalent adenoviral-vectored vaccines would be a viable next-generation vaccine strategy.
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Project description:The dire need for safe and effective coronavirus disease (COVID-19) vaccines is met with many vaccine candidates being evaluated in pre-clinical and clinical studies. The COVID-19 vaccine candidates currently in phase 3 or phase 2/3 clinical trials as well as those that recently received emergency use authorization (EUA) from the United States Food and Drug Administration (FDA) and/or other regulatory agencies worldwide require either cold (i.e., 2-8°C) or even freezing temperatures as low as -70°C for storage and distribution. Thus, existing cold chain will struggle to support both the standard national immunization programs and COVID-19 vaccination. The requirement for cold chain is now a major challenge towards worldwide rapid mass vaccination against COVID-19. In this commentary, we stress that thermostabilizing technologies are available to enable cold chain-free vaccine storage and distribution, as well as potential needle-free vaccination. Significant efforts on thermostabilizing technologies must now be applied on next-generation COVID-19 vaccines for more cost-effective worldwide mass vaccination and COVID-19 eradication.
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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 world is grappling with an unprecedented public health crisis COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2. Due to the high transmission/mortality rates and socioeconomic impacts of the COVID-19, its control is crucial. In the absence of specific treatment, vaccines represent the most efficient way to control and stop the pandemic. Many companies around the world are currently making efforts to develop the vaccine to combat COVID-19. This review outlines key strategies for generating SARS-CoV-2 vaccine candidates, along with the mechanism of action, advantages, and potential limitations of each vaccine. The use of nanomaterials and nanotechnology for COVID-19 vaccines development will also be discussed.
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Project description:BackgroundThis report summarizes the discussions and conclusions from the "Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID-19 Pandemic" meeting, which took place in Seattle, USA, from March 1, 2023, to March 3, 2023.ConclusionsDiscussions around influenza virus correlates of protection and their use continued from where the discussion had been left off in 2019. While there was not much progress in the influenza field itself, many lessons learned during the coronavirus disease 2019 (COVID-19) pandemic, especially the importance of mucosal immunity, were discussed and can directly be applied to influenza correlates of protection.
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Project description:Purpose: The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) of COVID-19 kidney to normal controls Methods/Results: Kidney mRNA profile of human COVID-19 tissue was generated by deep sequencing using Illumina Novaseq6000 Paired-end 150. After filtering reads mapped to contamination database, the reads that were uniquely aligned to the exon and splicing-junction segments with a maximal 2 mismatches for each transcript were then counted as expression level for corresponding transcript. Next, RNA-seq reads count data were downloaded from public resource GTEx project (https://www.gtexportal.org/home/datasets) and 12 normal kidney tissue samples were extracted as controls. The differential analysis by fold change difference was carried out to identify dysregulated genes at 1.5 fold change. The differential expressed genes were then subjected to Gene Ontology function and Pathway (KEGG, Ingenuity IPA, BIOCARTA, NABA, Panther, PID, REACTOME, Wiki-pathway) enrichment analysis by Fisher-exact test. Conclusions: RNA sequencing data revealed that biological processes from upregulated genes were enriched for cell cycle, chromosome segregation, response to wounding, humoral immune response, and blood coagulation, suggesting that cell injury/regeneration, inflammatory response, and endothelial injury were the major disease processes involved. The biological processes from downregulated genes were enriched for ion transport, metabolic processes, and oxidation, likely secondary to severe tubular cell injury. Pathway analysis from both up- and downregulated genes showed enrichment of transmembrane transport, oxidation, and blood coagulation consistent with the GO terms analysis. Upregulated genes were enriched only for the FOXM1 pathway, which was recently reported to promote tubular cell proliferation during injury repair. Additionally, genes related to the renin-angiotensin system were downregulated, but ACE2 expression did not differ from normal controls.
2021-08-09 | GSE157403 | GEO
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Project description:The novel coronavirus SARS-CoV-2 (causing the disease COVID-19) has caused a highly transmissible and ongoing pandemic worldwide. Due to its rapid development, next-generation sequencing plays vital roles in many aspects. Here, we summarize the current knowledge on the origin and human transmission of SARS-CoV-2 based on NGS analysis. The ACE2 expression levels in various human tissues and relevant cells were compared to provide insights into the mechanism of SAS-CoV-2 infection. Gut microbiota dysbiosis observed by metagenome sequencing and the immunogenetics of COVID-19 patients according to single-cell sequencing analysis were also highlighted. Overall, the application of these sequencing techniques could be meaningful for finding novel intermediate SARS-CoV-2 hosts to block interspecies transmission. This information will further benefit SARS-CoV-2 diagnostic development and new therapeutic target discovery. The extensive application of NGS will provide powerful support for our fight against future public health emergencies.
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