Dataset Information

BNT162b2 Vaccine Encoding the SARS-CoV-2 P2 S Protects Transgenic hACE2 Mice against COVID-19.

ABSTRACT: BNT162b2 is a highly efficacious mRNA vaccine approved to prevent COVID-19. This brief report describes the immunogenicity and anti-viral protective effect of BNT162b2 in hACE2 transgenic mice. Prime-boost immunization with BNT162b2 elicited high titers in neutralizing antibodies against SARS-CoV-2, which correlated with viral clearance and alleviated lung lesions in these mice after viral challenge.

SUBMITTER: Ji RR

PROVIDER: S-EPMC8066210 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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BNT162b2 Vaccine Encoding the SARS-CoV-2 P2 S Protects Transgenic hACE2 Mice against COVID-19.

Ji Rui-Ru RR Qu Yajin Y Zhu Hua H Yang Yumei Y Vogel Annette B AB Sahin Ugur U Qin Chuan C Hui Aimin A

Vaccines 20210401 4

BNT162b2 is a highly efficacious mRNA vaccine approved to prevent COVID-19. This brief report describes the immunogenicity and anti-viral protective effect of BNT162b2 in hACE2 transgenic mice. Prime-boost immunization with BNT162b2 elicited high titers in neutralizing antibodies against SARS-CoV-2, which correlated with viral clearance and alleviated lung lesions in these mice after viral challenge. ...[more]

PMID: 33915773

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Project description:Dysregulation of host metabolism is a feature of lethal SARS-CoV-2 infection. Perturbations in α-ketoglutarate levels can elicit metabolic reprogramming through 2-oxoglutarate-dependent dioxygenases (2-ODDGs), leading to stabilization of the transcription factor HIF-1α. HIF1-α activation has been reported to promote antiviral mechanisms against SARS-CoV-2 through direct regulation of ACE2 expression (a receptor required for viral entry). However, given the numerous pathways HIF-1α serves to regulate it is possible that there are other undefined metabolic mechanisms contributing to the pathogenesis of SARS-CoV-2 independent of ACE2 downregulation. In this study, we used in vitro and in vivo models in which HIF-1α modulation of ACE2 expression was negated, allowing for isolated characterization of the host metabolic response within SARS-CoV-2 disease pathogenesis. We demonstrated that SARS-CoV-2 infection limited stabilization of HIF-1α and associated mitochondrial metabolic reprogramming by maintaining activity of the 2-ODDG prolyl hydroxylases. Inhibition of 2-ODDGs with dimethyloxalylglycine promoted HIF-1α stabilization following SARS-CoV-2 infection, and significantly increased survival among SARS-CoV-2-infected mice compared with vehicle controls. However, unlike previous reports, the mechanism by which activation of HIF-1α responses contributed to survival was not through impairment of viral replication. Rather, dimethyloxalylglycine treatment facilitated direct effects on host metabolism including increased glycolysis and resolution of dysregulated pools of metabolites, which correlated with reduced morbidity. Taken together, these data identify (to our knowledge) a novel function of α-ketoglutarate-sensing platforms, including those responsible for HIF-1α stabilization, in the resolution of SARS-CoV-2 infection and support targeting these metabolic nodes as a viable therapeutic strategy to limit disease severity during infection.

Dataset Information

BNT162b2 Vaccine Encoding the SARS-CoV-2 P2 S Protects Transgenic hACE2 Mice against COVID-19.

Publications

BNT162b2 Vaccine Encoding the SARS-CoV-2 P2 S Protects Transgenic hACE2 Mice against COVID-19.

Similar Datasets

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