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Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2 [bulk VDJ-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. BCR-seq and TCR-seq unveiled repertoire diversity and clonal expansions in vaccinated animals.

ORGANISM(S): Mus musculus

PROVIDER: GSE201268 | 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 [scRNA-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 transcriptomics of WT- and variant-specific LNP-mRNA vaccinated animals revealed a systematic landscape of immune cell populations and global gene expression.

2022-04-25 | GSE201266 | GEO

Development of next-generation therapeutic antibodies using rapid mRNA immunization of humanized mice

Project description:We generated LNP-mRNAs encoding B.1.1.529 SARS-CoV-2 spike, or single transmembrane protein CD22, or GPCR GPRC5D, respectively. Those LNP-mRNAs were intramuscularly administered in a human IgG and IgK knock-in mouse. Single cell VDJ-seq unveiled the sequences of human monoclonal antibodies targeting those target antigens.

2023-10-01 | GSE215441 | GEO

Polyvalent mRNA vaccination elicited potent immune response to monkeypox surface antigens

Project description:The soaring global monkeypox cases lead to a surge in demand for monkeypox vaccine, which far exceeds the supply. mRNA vaccine has achieved great success in prevention of coronavirus disease and holds promise against diverse pathogens. In this study, we generate a polyvalent lipid nanoparticle (LNP) mRNA vaccine candidate for monkeypox virus (MPXV) and evaluate its immunogenicity in animal models. This polyvalent MPXV mRNA vaccine candidate, MPXVac-097, encodes five 2022 MPXV targets that are important surface antigens. Three-dose (prime-boost-booster) MPXVac-097 vaccination elicits strong antibody response to A35R and E8L antigens, moderate response to M1R, but not B6R or A29, highlighting the differences in immunogenicity. Bulk T cell receptor (TCR) sequencing reveals preferential usage of VJ combinations and clonal expansion of peripheral T cells after MPXVac-097 vaccination. These data demonstrate initial feasibility of developing MPXV mRNA vaccine and pave the way for its future optimization.

2023-02-13 | GSE225183 | GEO

Organism-level analysis of vaccination reveals networks of protection across tissues

Project description:To study the response of single lung and liver memory CD8+ T cells to reactivation, mice vaccinated subcutaneously with MVA (10^7 PFUs/mouse) were subsequently challenged intranasally with: (1) PBS; (2) WR (10^7 PFUs/mouse); or (3) Vaccinia virus-derived B8R20-27 peptide (20 µg/mouse). Sixteen hours after challenge, single-cell suspensions were generated from lung or liver and lymphocytes were enriched using Percoll density centrifugation prior to immunostaining and cell sorting. Single memory CD8+ T cells from lung and liver were profiled using plate-based or droplet-based single-cell RNA-seq.

2017-09-21 | GSE90697 | GEO

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.

2022-09-05 | GSE212586 | GEO

Profiling of human monoclonal antibodies targeting SARS-CoV-2 Omicron variant

Project description:We generated LNP-mRNA encoding B.1.1.529 SARS-CoV-2 spike, and intramuscularly administered it in a human IgG and IgK knock-in mouse. Single cell VDJ-seq unveiled the sequences of human monoclonal antibodies targeting the B.1.1.529 SARS-CoV-2 spike protein.

2022-07-01 | GSE203030 | GEO

DIVA Metabolomics: Differentiating Vaccination Status Following Viral Challenge Using Metabolomic Profiles

Project description:This study employed metabolomic profiling technologies, to identify metabolites (small molecules) in blood which are found at different levels in vaccinated compared to non-vaccinated animals exposed to virus.

2018-07-13 | MTBLS456 | MetaboLights

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

Systems biology of vaccination for seasonal influenza in humans

Project description:This SuperSeries is composed of the following subset Series: GSE29614: Time Course of Young Adults Vaccinated with Influenza TIV Vaccine during 2007/08 Flu Season GSE29615: Time Course of Young Adults Vaccinated with Influenza LAIV Vaccine during 2008/09 Flu Season GSE29617: Time Course of Young Adults Vaccinated with Influenza TIV Vaccine during 2008/09 Flu Season GSE29618: FACS-sorted cells from Young Adults Vaccinated with Influenza TIV or LAIV Vaccines during 2008/09 Flu Season Refer to individual Series

2011-07-10 | E-GEOD-29619 | biostudies-arrayexpress

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