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

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

PROVIDER: PRJNA830588 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18863610_1.fastq.gz	Fastqsanger.gz
	SRR18863610_2.fastq.gz	Fastqsanger.gz
	SRR18863611_1.fastq.gz	Fastqsanger.gz
	SRR18863611_2.fastq.gz	Fastqsanger.gz
	SRR18863612_1.fastq.gz	Fastqsanger.gz

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

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

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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.

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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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Project description:Vaccination against tuberculosis by intradermal Bacillus Calmette-Guérin (BCG) injection saves many lives, supposedly by inducing adaptive immune memory in lymphocytes. Epidemiologically, BCG vaccination is also associated with reduced childhood mortality unrelated to TB, which is attributed to innate immune memory, also termed trained immunity. We recently demonstrated improved protection against tuberculosis infection in highly susceptible rhesus macaques by mucosal BCG vaccination, correlating with a unique local but no peripheral immune profile. Here, we investigated local and peripheral innate immune function after intradermal versus mucosal vaccination with M. bovis BCG or the live attenuated, M. tuberculosis-derived candidate, MTBVAC. The results demonstrate an augmented frequency of trained immunity in monocytes after respiratory mucosal administration of live attenuated mycobacterial vaccines compared to intradermal immunization, with MTBVAC being equally potent as BCG. These results provide further support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.

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