Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1242379 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32869558_1.fastq.gz | Fastqsanger.gz | |||
| SRR32869559_1.fastq.gz | Fastqsanger.gz | |||
| SRR33471811_1.fastq.gz | Fastqsanger.gz | |||
| SRR33471811_2.fastq.gz | Fastqsanger.gz | |||
| SRR33471812_1.fastq.gz | Fastqsanger.gz |
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Project description:Influenza A viruses continue to evolve across avian and mammalian hosts, highlighting the need for vaccines that elicit broad and durable immunity. Here, we developed a modular live-attenuated influenza vaccine (LAIV) platform based on a short NS1 truncation (ΔNS1-86) engineered to express heterologous HA1 antigens through a multibasic-cleavage and 2A-peptide system. ΔNS1-86 LAIVs replicated in an attenuated manner while maintaining stable antigen expression. In mice, a single intranasal dose induced strong neutralizing antibodies and robust cross-reactive IFN-γ–producing T cell responses against divergent H5N1 clades and H9N2 lineages. In ferrets, the ΔNS1-86 LAIV provided sterilizing protection against a highly mammalian-adapted North American clade 2.3.4.4b H5N1 virus, completely blocking viral shedding and systemic dissemination—efficacy that surpassed a two-dose inactivated vaccine despite similar neutralization titers. The platform was adaptable to multiple HA/NA backbones and compatible with DIVA diagnostics. These findings establish ΔNS1-86 LAIVs as versatile candidates for broad influenza protection and pandemic preparedness.
2026-07-27 | GSE326254 | GEO
Project description:Background Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses are widely circulating in North America with unprecedented transmission into novel host species. A high incidence of neurologic disease is observed in carnivores infected with clade 2.3.4.4b HPAI H5N1 viruses and historical outbreaks of HPAI H5N1 in humans are also associated with neurologic complications, raising concerns about neurotropism and neurovirulence of clade 2.3.4.4b HPAI H5N1 viruses. Methods We analyzed virus replication kinetics, cellular tropism, and host responses to infection in human cerebral organoids (hCOs) inoculated with clade 2.3.4.4b HPAI H5N1 viruses compared to a historical clade 1 HPAI H5N1 virus and a seasonal influenza A virus. Results HPAI H5N1 viruses replicated to high titers in hCOs, but replication of the seasonal influenza A virus was not detected. Viral antigen and RNA were detected primarily in neuron- and astrocyte-like cells. Interferon responses to infection with HPAI H5N1 viruses were observed in a small population of bystander cells. Higher levels of cell death and proinflammatory cytokines and chemokines were observed in organoids inoculated with the historical HPAI H5N1 isolate. Conclusions Clade 2.3.4.4b HPAI H5N1 viruses exhibit similar neurotropism compared to a historical clade 1 HPAI H5N1 virus. Lower levels of cell death and inflammatory cytokine production induced by clade 2.3.4.4b viruses may indicate reduced neuropathogenic potential of these viruses in humans.
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Project description:The unexpected circulation of clade 2.3.4.4b H5N1 influenza viruses in dairy cattle and the transmission to diverse mammalian species poses a pandemic risk. We sought to explore cattle and human respiratory susceptibility to the 2.3.4.4b H5N1 virus. We establish long-term expandable cattle airway and mammary organoids. The 2.3.4.4b H5N1 virus exhibits high replicative fitness in cattle mammary organoids, recapitulating its remarkable mammary tropism. The virus also replicates robustly in cattle airway organoids, suggesting an underrecognized respiratory component in ongoing outbreaks. Interestingly, human airway and nasal organoids are highly susceptible to the 2.3.4.4b H5N1 virus. Yet, a novel organoid-based neutralization assay reveals that N1 antibodies in human sera had cross-neutralizing activity against the 2.3.4.4b H5N1 and ancestral H5N1-VN1194 viruses. The cross-neutralization, exclusively manifested in the organoid-based assay, is enhanced after seasonal influenza vaccination and diminished after depleting N1-specific antibodies. Therefore, cross-neutralizing N1 antibodies are likely limiting zoonotic infection by H5N1 viruses in humans.
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