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Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2 [scRNA-seq]

ABSTRACT: We generated LNP-mRNAs specifically encoding wildtype (WT), B.1.351 and B.1.617 SARS-CoV-2 spikes, and systematically studied their immune responses. Single cell transcriptomics of WT- and variant-specific LNP-mRNA vaccinated animals revealed a systematic landscape of immune cell populations and global gene expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE201266 | GEO | 2022/04/25

REPOSITORIES: GEO

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Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2 [scVDJ-seq]

Project description:We generated LNP-mRNAs specifically encoding wildtype (WT), B.1.351 and B.1.617 SARS-CoV-2 spikes, and systematically studied their immune responses. Single cell BCR-seq and TCR-seq unveiled repertoire diversity and clonal expansions in vaccinated animals.

2022-04-25 | GSE201267 | GEO

Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2 [bulk VDJ-seq]

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Systems biology of vaccination for seasonal influenza in humans

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BCG vaccination of mice elicits transcriptional changes in blood that predict protection against M.tb. challenge

Project description:Although BCG has been used for almost 100 years to immunize against Mycobacterium tuberculosis, TB remains a global public health threat. Numerous clinical trials are underway studying novel vaccine candidates and strategies to improve or replace BCG, but vaccine development still lacks a well-defined set of immune correlates to predict vaccine-induced protection against tuberculosis. This study aimed to address this gap by examining transcriptional responses to BCG vaccination in C57BL/6 inbred mice, coupled with protection studies using Diversity Outbred mice. We evaluated relative gene expression in blood obtained from vaccinated mice, because blood is easily accessible and data can be translated to human studies. We first determined that the average peak time after vaccination is 14 days for gene expression of a small subset of immune-related genes in inbred mice. We then performed global transcriptomic analyses using whole blood samples obtained two weeks after mice were vaccinated with BCG. Using comparative bioinformatic analyses and qRT-PCR validation, we developed a working correlate panel of 18 genes that were highly correlated with administration of BCG but not heat-killed BCG. We then tested this gene panel using BCG-vaccinated Diversity Outbred mice and revealed associations between the expression of a subset of genes and disease outcomes after aerosol challenge with M. tuberculosis. These data therefore demonstrate that blood-based transcriptional immune correlates measured within a few weeks after vaccination can be derived to predict protection against M. tuberculosis, even in outbred populations.

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Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-04-25 | GSE201269 | GEO

Humoral or Cellular Immunity Induced by RNA Vaccine Protects IFNAR-/- Mice against Crimean-Congo Hemorrhagic Fever Virus Infection

Project description:Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is on the World Health Organizations list over emerging pathogens and prioritized diseases. With global distribution, high fatality rate and no approved treatment or vaccine, CCHF constitute a treat against the global health. In the current study we show full protection of mice against lethal CCHFV infection due to mRNA-LNP vaccination. IFNAR-/- mice received two immunizations with either mRNA-LNP encoding for the CCHFV nucleoprotein, glycoproteins or a combination of both. While unvaccinated mice showed clear signs of severe disease, vaccinated mice was significantly protected. Vaccine induced immune responses due to vaccination was evaluated both in IFNAR-/- and immunocompetent mice and a strong humoral and cellular immune response was observed in both mouse models with high titers of neutralizing antibodies and primed T-cells. In addition, we conducted a proteomic analysis on liver samples from vaccinated and unvaccinated mice after CCHFV infection to determine the effect of vaccination on the protein profile. Similar to what has been observed in humans due to vaccination, there was an effect on metabolic pathways. In conclusion, this study shows very promising results regarding development of a vaccine against CCHFV.

2021-11-15 | PXD023300 | Pride

Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2.

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| S-EPMC9040489 | biostudies-literature

Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2

Project description:Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2

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A Cell-based Systems Biology Assessment of Human Blood to Monitor Immune Responses After Influenza Vaccination

Project description:Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses. PBMC and six purified cell types from two vaccinated donors were isolated prior to (d0) and at days 1, 3, and 7 post-TIV vaccination for RNA-seq analysis

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Project description:The result show that an mRNA/LNP vaccine induced significant numbers of differentially expressed genes (DEG). The analysis identified 123 DEGs between control PBS and mRNA/LNP vaccinated groups where 23 genes and 100 genes were upregulated and downregulated, respectively, in the mRNA/LNP group. To understand the biological changes from the transcriptomic data, gene set enrichment analysis (GSEA) was performed using the whole transcriptome data set. GSEA identified the biological pathways associated with interferon gamma response and protein secretion as the top two ‘Hallmark’ gene sets enriched in OVA mRNA/LNP group, compared to PBS group.

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