Experimental spillover of H5N1 clade 2.3.4.4b high pathogenicity avian influenza virus from gulls to minks reveals mammalian adaptation without spillback potential
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PROVIDER: PRJEB95805 | ENA |
REPOSITORIES: ENA
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Project description:The H5N1 avian influenza virus clade 2.3.4.4b outbreak represents a major pandemic threat for humans. Although most human cases to date have been mild, several severe cases of respiratory illness have been reported. A key unanswered question is the pathogenesis of H5N1 infection in primates following respiratory infection. In this study, we observed severe clinical disease in cynomolgus and rhesus macaques following respiratory infection with the H5N1 isolate A/Texas/37/2024 (hu-TX37-H5N1). Cynomolgus macaques inoculated with a high dose of hu-TX37-H5N1 developed severe consolidative necrotizing pneumonia with extrapulmonary spread. Clinical disease was rapidly progressive and lethal in 100% (9 of 9) of macaques by day 5-9 following challenge. Rhesus macaques inoculated with varying doses of hu-TX37-H5N1 demonstrated dose-dependent mortality, and surviving animals showed robust natural protective immunity against high dose re-challenge. H5N1 infection in both cynomolgus and rhesus macaques was characterized by upregulation of proinflammatory cytokine, innate immune cell, complement and coagulation, apoptosis, and immune exhaustion pathways and downregulation of NK, T, and B cell activation and differentiation pathways. Taken together, our data demonstrate severe respiratory disease with H5N1 clade 2.3.4.4b in nonhuman primates and suggest that acute inflammation and immune dysregulation are key contributors to disease pathogenesis.
2025-08-01 | GSE287709 | GEO
Project description:Lethal Disease Following H5N1 Avian Influenza Virus Clade 2.3.4.4b Infection in Macaques
| PRJNA1214282 | ENA
Project description:Over the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, and yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a systems biology method called weighted gene correlation network analysis (WGCNA) to identify and statistically validate signaling sub-networks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). A detailed examination of two sub-networks involved in the immune response and keratin filament formation revealed potential novel mediators of HPAI H5N1 pathogenesis, and additional experiments validated upregulation of these transcripts in response to VN1203 infection in C57BL/6 mice. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection, and identify novel avenues for perturbation studies and potential therapeutic intervention of fatal HPAI H5N1 disease.
2011-09-02 | GSE28166 | GEO
Project description:U.S. H5N1 clade 2.3.4.4b genotype B3.13 immediate releases related to emergence and spread in dairy cattle
| PRJNA1102327 | ENA
Project description:Messenger RNA vaccines based on lipid nanoparticles (mRNA-LNPs) are promising vaccine modalities. However, mRNA-LNP vaccines frequently cause adverse reactions such as swelling and fever in humans, partly due to the inflammatory nature of LNP. Modification of the ionizable lipids used in LNP is one approach to avoid these adverse reactions. Herein, we report the development of mRNA-LNP vaccines with better protective immunity and reduced adverse reactions using LNP, including SS-cleavable and pH-activated lipid-like materials with oleic acid (ssPalmO) as an ionizable lipid (LNPssPalmO). We used mRNA expressing H5N1 subtype high-pathogenicity avian influenza virus-derived hemagglutinin or neuraminidase to generate mRNA-LNP vaccines against H5N1 influenza. Compared with conventional LNP, mRNA-LNPssPalmO induced comparable antigen-specific antibodies and better IFN--producing Th1 responses in mice. Both mRNA-LNPssPalmO and conventional mRNA-LNP conferred strong protection against homologous H5N1 virus challenge. In addition, mRNA-LNPssPalmO showed better cross-protection against heterologous H5N1 virus challenge compared to conventional mRNA-LNPs. Furthermore, we observed that mRNA-LNPssPalmO induced less inflammatory responses (e.g., inflammatory cytokine production and vascular hyperpermeability) and fewer adverse reactions (e.g., weight loss and fever) compared with conventional mRNA-LNP. These results suggest that mRNA-LNPssPalmO would be a safe alternative to conventional vaccines to overcome mRNA-LNP vaccine hesitancy.
2025-03-05 | GSE279743 | GEO
Project description:Messenger RNA vaccines based on lipid nanoparticles (mRNA-LNPs) are promising vaccine modalities. However, mRNA-LNP vaccines frequently cause adverse reactions such as swelling and fever in humans, partly due to the inflammatory nature of LNP. Modification of the ionizable lipids used in LNP is one approach to avoid these adverse reactions. Herein, we report the development of mRNA-LNP vaccines with better protective immunity and reduced adverse reactions using LNP, including SS-cleavable and pH-activated lipid-like materials with oleic acid (ssPalmO) as an ionizable lipid (LNPssPalmO). We used mRNA expressing H5N1 subtype high-pathogenicity avian influenza virus-derived hemagglutinin or neuraminidase to generate mRNA-LNP vaccines against H5N1 influenza. Compared with conventional LNP, mRNA-LNPssPalmO induced comparable antigen-specific antibodies and better IFN--producing Th1 responses in mice. Both mRNA-LNPssPalmO and conventional mRNA-LNP conferred strong protection against homologous H5N1 virus challenge. In addition, mRNA-LNPssPalmO showed better cross-protection against heterologous H5N1 virus challenge compared to conventional mRNA-LNPs. Furthermore, we observed that mRNA-LNPssPalmO induced less inflammatory responses (e.g., inflammatory cytokine production and vascular hyperpermeability) and fewer adverse reactions (e.g., weight loss and fever) compared with conventional mRNA-LNP. These results suggest that mRNA-LNPssPalmO would be a safe alternative to conventional vaccines to overcome mRNA-LNP vaccine hesitancy.
2025-03-05 | GSE279744 | GEO
Project description:Over the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, and yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a systems biology method called weighted gene correlation network analysis (WGCNA) to identify and statistically validate signaling sub-networks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). A detailed examination of two sub-networks involved in the immune response and keratin filament formation revealed potential novel mediators of HPAI H5N1 pathogenesis, and additional experiments validated upregulation of these transcripts in response to VN1203 infection in C57BL/6 mice. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection, and identify novel avenues for perturbation studies and potential therapeutic intervention of fatal HPAI H5N1 disease. Calu-3 cells were infected with VN1203 influenza virus and profiled at 0, 3, 7, 12, 18, and 24 hours post infection. There are 3 mock and infected replicates for each time point.
2011-09-01 | E-GEOD-28166 | biostudies-arrayexpress
Project description:While infection of chickens with highly pathogenic avian influenza (HPAI) H5N1 subtypes often leads to complete mortality within 24 to 48 h, infection of ducks in contrast causes mild or no clinical signs. Rapid onsets of fatal disease in chickens, but with no evidence of severe clinical symptoms in ducks, suggest underlying differences in their innate immune mechanisms. To understand the molecular basis for such difference, chicken and duck primary lung cells, infected with a low-pathogenicity avian influenza (LPAI) and two HPAI H5N1 viruses, were subjected to RNA expression profiling using Affymetrix Chicken GeneChip arrays. We used microarrays to analyze the gene expression profiles of primary chicken and duck lung cells infected with H2N3 LPAI and two H5N1 influenza virus subtypes to understand the molecular basis of host susceptibility and resistance. We have identified a set of key genes and pathways that could play an important role in mediating innate host resistance to avian influenza in chickens and ducks.
2014-12-04 | GSE33389 | GEO
Project description:While infection of chickens with highly pathogenic avian influenza (HPAI) H5N1 subtypes often leads to complete mortality within 24 to 48 h, infection of ducks in contrast causes mild or no clinical signs. Rapid onsets of fatal disease in chickens, but with no evidence of severe clinical symptoms in ducks, suggest underlying differences in their innate immune mechanisms. To understand the molecular basis for such difference, chicken and duck primary lung cells, infected with a low-pathogenicity avian influenza (LPAI) and two HPAI H5N1 viruses, were subjected to RNA expression profiling using Affymetrix Chicken GeneChip arrays. We used microarrays to analyze the gene expression profiles of primary chicken and duck lung cells infected with H2N3 LPAI and two H5N1 influenza virus subtypes to understand the molecular basis of host susceptibility and resistance. We have identified a set of key genes and pathways that could play an important role in mediating innate host resistance to avian influenza in chickens and ducks. 24 hours following infection, total RNA from cells was extracted. Replicate RNA samples from each of the virus-infected (H2N3, H5N1 50-92, or H5N1 ty-Ty) or mock-infected chicken and duck cells (4 treatment groups for each species) were used for microarray analysis. Each of the RNA samples was hybridized to one GeneChipM-BM-. Chicken Genome Array (Affymetrix), and a total of 16 array chips were used.
2014-12-04 | E-GEOD-33389 | biostudies-arrayexpress