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A feature selection model identifies early blood transcripts predicting vaccine induced protection against influenza (HA PR8 antigen)

ABSTRACT: Seasonal influenza viruses cause an annual mortality of 300,000 to 600,000. Influenza viruses further give rise to pandemics which may cause millions of deaths. Vaccination is the most important measure to protect the population. However, non- or low responders to influenza vaccines are common and found to account for approximately 10% of vaccinees. Here, we investigated the use of early transcriptional data to predict influenza vaccine effectiveness. Mice were vaccinated with a single dose of influenza HA from the A/Puerto Rico/8/1934 (PR8) strain, administered alone or formulated in different adjuvants, and blood samples were collected for single-cell RNA sequencing at day 4 post-immunization. A feature selection model, based on random forest algorithms, was developed to identify vaccine-induced genes linked to protection from influenza challenge using the homologous PR8 strain. Several genes were consistently associated with disease severity, with some genes correlating positively and others negatively with disease outcome. The model also predicted the disease severity in an independent experiment using a heterologous challenge, demonstrating its robustness. These findings highlight the potential of using early biomarkers to identify non- or low responders to vaccination. Biomarkers may also guide vaccine studies, potentially optimizing vaccine development and reducing development costs.

ORGANISM(S): Mus musculus

PROVIDER: GSE283066 | GEO | 2026/06/01

REPOSITORIES: GEO

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A feature selection model identifies early blood transcripts predicting vaccine induced protection against influenza (HA0 A/California/04/2009 antigen)

Project description:Seasonal influenza viruses cause an annual mortality of 300,000 to 600,000. Influenza viruses further give rise to pandemics which may cause millions of deaths. Vaccination is the most important measure to protect the population. However, non- or low responders to influenza vaccines are common and found to account for approximately 10% of vaccinees. Here, we investigated the use of early transcriptional data to predict influenza vaccine effectiveness. Mice were vaccinated with a single dose of influenza HA from the A/Puerto Rico/8/1934 (PR8) strain, administered alone or formulated in different adjuvants, and blood samples were collected for single-cell RNA sequencing at day 4 post-immunization. A feature selection model, based on random forest algorithms, was developed to identify vaccine-induced genes linked to protection from influenza challenge using the homologous PR8 strain. Several genes were consistently associated with disease severity, with some genes correlating positively and others negatively with disease outcome. The model also predicted the disease severity in an independent experiment using a heterologous challenge, demonstrating its robustness. These findings highlight the potential of using early biomarkers to identify non- or low responders to vaccination. Biomarkers may also guide vaccine studies, potentially optimizing vaccine development and reducing development costs.

2026-06-01 | GSE283065 | GEO

Immunosignatures can predict vaccine efficacy

2013-11-04 | GSE51623 | GEO

Immunosignatures can predict vaccine efficacy

Project description:Mice were immunized with either formalin fixed Influenza A/PR/8/34 (Killed PR8), the 2006-2007 seasonal influenza vaccine, the 2007-2008 seasonal influenza vaccine, a sublethal infection (live PR8) or mock immunized (PBS). Array data was used to distinguish the immunogens from each other and predict which of the three inactivated vaccines would be protective against A/PR/8/34 challenge. two replicates of each peptide was printed on 1 CIM_10kv3 peptide microarray. One microarray were tested for each sample. Image was qualified using in-house metrics for quality assurance.

2013-11-04 | E-GEOD-51623 | biostudies-arrayexpress

Identification of a cryptic MHC-E epitope from influenza virus

Project description:B6-CIITA-E cell line (C57Bl/6 fibroblasts expressing MHC-II molecules I-Ab and I-Ed) was infected with Influenza A virus (A/Puerto Rico/8/1934, PR8) or left uninfected (control), and the MHC-class II-associated peptidome analysed via immunopeptidomics.

2023-10-10 | PXD045025 | Pride

Obese individuals exhibit distinct temporal gene expression dynamics in response to influenza vaccination

Project description:The effectiveness of the seasonal influenza vaccine varies between individuals. Specific risk groups with comorbidities, such as the obese, have an increased risk of infection even when vaccinated. It has been proposed that a heightened baseline inflammatory state and alterations in adaptive immune cell populations in obese individuals may adversely impact immune response to pathogens and vaccines. Therefore, understanding differences in vaccine response in obese individuals is critical for the development of improved influenza vaccine design and strategies. Previously, we identified a transcriptomic signature prior to seasonal influenza vaccination that is predictive of an individual’s response to the influenza vaccine. To understand the dynamics of the host response following vaccination we studied systemic gene expression from whole blood collected from 163 vaccinated individuals on days 3, 7, and 28 post-vaccination. Gene expression profiles were compared between high and low vaccine responders in both obese and non-obese groups. We detected characteristic changes in gene expression over time, with a peak at day 7 post-vaccination. A large subset of genes associated with the adaptive immune response exhibited significantly different expression in high- and non- vaccine responders. Distinct gene sets presented differing temporal patterns in different weight and response groups, indicative of molecular processes impacting the immune response to vaccination.

2025-06-25 | GSE271520 | GEO

Transcriptional and Immunologic Correlates of Response to Pandemic Influenza Vaccine in Aviremic, HIV-Infected Children

Project description:People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and >13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5, a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups.

2021-03-18 | GSE167893 | GEO

Highly pathogenic influenza virus inhibit Inflammatory Responses in Monocytes via Activation of the Rar-Related Orphan Receptor Alpha (RORalpa)

Project description:Highly pathogenic influenza virus inhibit Inflammatory Responses in Monocytes via Activation of the Rar-Related Orphan Receptor Alpha (RORalpha). Low (PR8) and high pathogenic influenza viruses (FPV and H5N1) were used. Monocytes were infected with low (PR8) and high pathogenic influenza viruses (FPV and H5N1)

2013-07-01 | E-GEOD-35283 | biostudies-arrayexpress

mRNA-based influenza vaccine expands the breadth of the B cell response in humans

Project description:Eliciting durable antibody responses against rapidly evolving pathogens such as the influenza virus remains a formidable challenge. Conventional influenza virus vaccines are poorly immunogenic and induce antibody responses of limited breadth. Germinal center (GC) reactions in draining lymph nodes are key sites for antibody diversification and affinity maturation following vaccination. Whether an mRNA-based influenza virus vaccine can induce a superior GC response in humans compared to conventional vaccines remains unclear. We assessed B cell responses in an observational study of cohorts of healthy young adults receiving a licensed, split-virion or an investigative mRNA-based quadrivalent seasonal influenza virus vaccine over two consecutive seasons. mRNA-based vaccines consistently elicited higher antibody titers and frequencies of memory B cells. In the draining lymph nodes, mRNA vaccination stimulated sustained GC reactions that persisted for at least 26 weeks post vaccination in five of thirteen participants across the two seasons. To understand how sustained GC activity shapes the secreted serum IgG repertoire, we performed proteomic analysis of serum IgG repertoire. mRNA vaccination increased the number of vaccine-elicited serum IgG clonotypes and promoted intraclonal expansion within pre-existing clonotypes. B cell lineage analyses further indicated that expanded serum clonotypes map to GC B cell-associated subbranches, consistent with ongoing GC-driven evolution underlying intraclonal expansion. This repertoire remodeling was accompanied by increased binding breadth against antigenically divergent influenza viruses. These findings reveal a key role for persistent GC responses in broadening the repertoire of vaccine-induced antibodies.

2026-04-18 | GSE328165 | GEO

Transcriptome-wide identification of the influenza A virus endoribonuclease PA-X cut sites by 5' RACE-Seq

Project description:Influenza A virus induces host shutoff mainly through its endoribonuclease PA-X. Like many host shutoff nucleases, PA-X activity affects different host RNAs to varying degrees. To understand how PA-X discriminates between different mRNAs, we took a high-throughput approach to directly identify PA-X cut sites transcriptome-wide and examine PA-X cleavage characteristics. To do this, we compared RNA fragments from mock infected cells to cells infected with the wild-type (WT) A/PuertoRico/8/1934 H1N1 (PR8) influenza virus strain, or the same strain engineered to lack PA-X, referred to as PR8-PA(∆X).

2023-04-20 | GSE207253 | GEO

Highly Pathogenic Avian Influenza Viruses Avoid Effective Inflammatory Response of Human Macrophages

Project description:Macrophages were infected with low (PR8) and high pathogenic influenza viruses (FPV and H5N1). To our surprise a genome-wide comparative systems biology approach revealed that in contrast PR8 infections with HPAIV H5N1 and FPV result in a reduced immune response of human macrophages contradicting a primary role of this cell type for the cytokine storm. Our data point to a viral strategy of HPAIV to bypass a major amplifier of the initial local inflammatory response thereby hampering antiviral effector mechanisms and facilitating virus spreading and systemic disease. Macrophages were infected with low (PR8) and high pathogenic influenza viruses (FPV and H5N1)

2012-05-28 | E-GEOD-27702 | biostudies-arrayexpress

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