Adenovirus 5 Vectors Expressing SARS-CoV-2 Proteins

Bachus, Scott; Akkerman, Nikolas; Fulham, Lauren; Graves, Drayson; Stephanson, Caelan; Memon, Harram; Miller, Matthew S.; Pelka, Peter

doi:10.1128/msphere.00998-21

Cited by 3 publications

(3 citation statements)

References 20 publications

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“…Viruses used in the study were Ad.CMV, Ad.ARGLU1, and Ad.ISceI and these were generated in-house by homologous recombination as previously described ( 24 ). HAdV dl 309 was previously described ( 25 ), dl 520 and pm 975 were also previously described ( 26 , 27 ).…”

Section: Methodsmentioning

confidence: 99%

“…Viral genomic DNA was purified using BioBasic DNA purification kit. Viral particles were quantified by quantitative real-time PCR, with a serial dilution of pXC1 plasmid (having the E1 region cloned in it) serving as the standard curve as previously described ( 24 ) using the BioRad CFX96 real-time thermocycler (BioRad) as described below in the real-time gene expression analysis section.…”

Section: Methodsmentioning

confidence: 99%

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ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair

Bachus,

Akkerman,

Fulham

et al. 2024

Nucleic Acids Research

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Arginine and glutamate rich 1 (ARGLU1) is a poorly understood cellular protein with functions in RNA splicing and transcription. Computational prediction suggests that ARGLU1 contains intrinsically disordered regions and lacks any known structural or functional domains. We used adenovirus Early protein 1A (E1A) to probe for critical regulators of important cellular pathways and identified ARGLU1 as a significant player in transcription and the DNA damage response pathway. Transcriptional effects induced by ARGLU1 occur via enhancement of promoter-proximal RNA polymerase II pausing, likely by inhibiting the interaction between JMJD6 and BRD4. When overexpressed, ARGLU1 increases the growth rate of cancer cells, while its knockdown leads to growth arrest. Significantly, overexpression of ARGLU1 increased cancer cell resistance to genotoxic drugs and promoted DNA damage repair. These results identify new roles for ARGLU1 in cancer cell survival and the DNA damage repair pathway, with potential clinical implications for chemotherapy resistance.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair

Bachus,

Akkerman,

Fulham

et al. 2024

Nucleic Acids Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Viral genomic DNA was then purified using BioBasic DNA purification kit. Viral genomes were then quantified by quantitative real-time PCR with a serial dilution of pXC1 plasmid (having the E1 region cloned in it) serving as the standard curve as previously described [ 49 ] using the BioRad CFX96 real-time thermocycler (BioRad).…”

Section: Methodsmentioning

confidence: 99%

HBO1/KAT7/MYST2 HAT complex regulates human adenovirus replicative cycle

Kamel,

Shete,

Gadamsetty

et al. 2024

Heliyon

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Intranasal delivery of a recombinant adenovirus vaccine encoding the PEDV COE elicits potent mucosal and systemic antibody responses in mice

Yan,

Luo,

Zhan

et al. 2024

Microbiol Spectr

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Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus that causes substantial economic loss to the global pig industry. The emergence of PEDV variants has increased the need for new vaccines, as commercial vaccines confer inferior protection against currently circulating strains. It is well established that the induction of mucosal immunity is crucial for PEDV vaccines to provide better protection against PEDV infection. In this study, we constructed a recombinant adenovirus expressing the core neutralization epitope (COE) of G2b PEDV based on human adenovirus serotype 5 (Ad5). We evaluated the effects of different administration routes and doses of vaccine immunogenicity in Balb/c mice. Both intramuscular (IM) and intranasal (IN) administration elicited significant humoral responses, including COE-specific IgG in serum and mucosal secretions, along with serum-neutralizing antibodies. Moreover, IN delivery was more potent than IM in stimulating IgA in serum and mucosal samples and in dampening the immune response to the Ad5 vector. The immune response was stronger after high versus low dose IM injection, whereas no significant difference was observed between high and low IN doses. In summary, our findings provide important insights for developing novel PEDV vaccines. IMPORTANCE Porcine epidemic diarrhea (PED) is a highly contagious disease that has severe economic implications for the pork industry. Developing an effective vaccine against PEDV remains a necessity. Here, we generated a recombinant adenovirus vaccine based on Ad5 to express the COE protein of PEDV (rAd5-PEDV-COE) and systematically evaluated the immunogenicity of the adenovirus-vectored vaccine using different administration routes (intramuscular and intranasal) and doses in a mouse model. Our results show that rAd5-PEDV-COE induced potent systemic humoral response regardless of the dose or immunization route. Notably, intranasal delivery was superior to induce peripheral and mucosal IgA antibodies compared with intramuscular injection. Our data provide valuable insights into designing novel PEDV vaccines.

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Adenovirus 5 Vectors Expressing SARS-CoV-2 Proteins

Cited by 3 publications

References 20 publications

ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair

ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair

HBO1/KAT7/MYST2 HAT complex regulates human adenovirus replicative cycle

Intranasal delivery of a recombinant adenovirus vaccine encoding the PEDV COE elicits potent mucosal and systemic antibody responses in mice

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