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Heterologous immunization combining vector- and mRNA-based vaccine elicits both robust innate and adaptive immune responses

ABSTRACT: Heterologous immunization combining vector- and mRNA-based vaccine elicits both robust innate and adaptive immune responses

PROVIDER: PRJNA1189001 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31429179_1.fastq.gz	Fastqsanger.gz
	SRR31429179_2.fastq.gz	Fastqsanger.gz
	SRR31429180_1.fastq.gz	Fastqsanger.gz
	SRR31429180_2.fastq.gz	Fastqsanger.gz
	SRR31429181_1.fastq.gz	Fastqsanger.gz

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Heterologous immunization combining vector- and mRNA-based vaccine elicits both robust innate and adaptive immune responses

Project description:Heterologous vaccination regimens are increasingly recommended for their potential benefits, including reduced side effects and enhanced immunogenicity. In this study, we investigated the innate and adaptive immune responses elicited by heterologous prime-boost vaccination using adenoviral vector and mRNA vaccines against SARS-CoV-2 in a mouse model. Our findings show that heterologous vaccination induced superior serum neutralizing and binding antibody titers, as well as enhanced cellular immune responses against the Delta and Omicron (BA.5) variants, compared to homologous vaccination. Single-cell transcriptomic analysis at the injection site, conducted 16 hours post-vaccination, revealed that the lipid nanoparticle (LNP)-based mRNA vaccine—and even empty LNP injection—triggered significant immune cell infiltration, while adenoviral vector vaccination caused minimal changes in injection-site cell composition following the first dose. Notably, spike mRNA was predominantly expressed in fibroblasts and macrophages across both vaccine platforms, suggesting these cells’ role in local immune responses. Further analysis demonstrated that the adenoviral vector booster induced amplified immune responses, marked by increased transcriptional changes, particularly in stromal pro-inflammatory pathways. Heterologous vaccination (adenoviral prime, mRNA boost) further intensified these responses compared to homologous mRNA vaccination, indicating that adenoviral priming enhances inflammatory responses when followed by an mRNA boost. In summary, our results demonstrate that heterologous vaccination strategies elicit stronger innate and adaptive immune responses compared to homologous regimens, supporting their use as an effective approach for enhanced protection against variants.

2025-01-23 | GSE282488 | GEO

Heterologous immunization with inactivated vaccine followed by mRNA booster elicits strong humoral and cellular immune responses against the SARS-CoV-2 Omicron variant

Project description:Heterologous vaccination for COVID19

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Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [RNA_seq]

Project description:Heterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than two doses of BNT162b2. Yet, the molecular transcriptome, the germline allelic variants of immunoglobulin loci and anti-Omicron antibody levels induced by the heterologous vaccination have not been formally investigated. Moreover, there is a paucity of COVID-19 vaccine studies including diverse genetic populations. Here, we show a robust molecular immune transcriptome and antibody repertoire in 46 office and lab workers from the Republic of Korea after heterologous vaccination, ChAdOx1 followed by BNT162b2. Anti-spike-specific IgG antibody levels against the ancestral SARS-CoV-2 strain increased from 70 AU/ml immediately following the first vaccination to 14,000 U/ml within three days after the second vaccination and 142,000 AU/ml after seven days. Antibody titers against more recent variants, including Omicron, were two- to three-fold lower, yet higher than those obtained after the second dose of a BNT162b2-BNT162b2 homologous vaccination. RNA-seq conducted on peripheral immune cells demonstrated a strong activation of interferon-induced genetic programs in the heterologous cohort and an increase of specific IGHV clonal transcripts encoding neutralizing antibodies was detected. Enrichment of B cell and CD4+ T cell responses was observed following both ChAdOx1-BNT162b2 heterologous and BNT162b2-BNT162b2 homologous vaccination using scRNA-seq, but clonally expanded memory B cells were relatively stronger in the heterologous cohort. In summary, a heterologous vaccination with ChAdOx1 followed by BNT162b2 provides an innate and adaptive immune response exceeding that seen in homologous BNT162b2 vaccination.

2022-05-20 | GSE201533 | GEO

Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [scRNA-seq]

2022-05-20 | GSE201534 | GEO

Cytomegalovirus vaccine vector-induced effector memory CD4+ T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza

Project description:To investigate the transcriptional response in whole blood from administration of the Cytomegolovirus vaccine vector against heterologous avian flu

2024-05-24 | GSE268204 | GEO

Expression data from CD8 memory T cells after IN immunization compared to IM immunization

Project description:Intranasal (IN) immunization induces different genotype expression in CD8 memory T cells compared to the CD8 memory T cells induced by intramuscular (IM) immunization. We used microarrays to detail the global program of gene expression underlying the differential induction after IN or IM immunization.

2017-01-28 | GSE77366 | GEO

Heterologous ChAdOx1-BNT162b2 vaccination in Korean cohort induces robust immune and antibody responses that includes Omicron

Project description:Heterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than BNT162b2-BNT162b2. Here we investigated the molecular transcriptome, germline allelic variants of immunoglobulin loci, and anti-Omicron antibody levels in 46 office and lab workers from the Republic of Korea following ChAdOx1-BNT162b2 vaccination. Anti-spike-specific IgG antibody levels against the ancestral SARS-CoV-2 strain increased from 70 AU/ml to 14,000 AU/ml to 142,000 AU/ml one, three and seven days following the second vaccination. Titers against VOC, including Omicron, were two- to three-fold lower, yet higher than those measured following BNT162b2-BNT162b2 vaccination. RNA-seq of peripheral immune cells demonstrated activation of interferon pathways with increased IGHV clonal transcripts encoding neutralizing antibodies. scRNA-seq revealed enriched B cell and CD4+ T cell responses in both ChAdOx1-BNT162b2 and BNT162b2-BNT162b2 recipients, but a stronger clonal expansion of memory B cells with ChAdOx1-BNT162b2. In summary, heterologous ChAdOx1-BNT162b2 provides an innate and adaptive immune response that exceeds homologous BNT162b2 vaccination.

2022-05-20 | GSE201535 | GEO

Whole blood RNAseq of SIVmac239-infected Mamu-B*08+/- indian rhesus macaques with and without heterologous adenovirus-vector SIV vaccination

Project description:Investigation of the transcriptional response in whole blood following SIVmac239 infection in Macaca mulatta vaccinated with heterologous prime-boost adenovirus-vector SIVmac239 Vif and Nef.

2024-10-07 | GSE272837 | GEO

Heterologous Microarray Hybridization Between Vesicomyid Symbionts

Project description:The goal of this study was to use heterologous microarray hybridization to determine genomic content shared among different vesicomyid symbionts. These symbionts are closely related and can be thought of as different strains of bacteria, facilitating the use of heterologous microarray hybridization to determine genomic content. Keywords: comparative genomic hybridization

2008-11-28 | GSE13447 | GEO

Multinodality vaccination against clade C SHIV: partial protection against mucosal challenges with a heterologous tier 2 virus

Project description:We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. We immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses.

2014-08-14 | GSE60368 | GEO

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