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There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442907 | PMC |
http://dx.doi.org/10.1126/sciadv.abg7996 | DOI Listing |
J Med Virol
August 2025
NHC Key Laboratory of Comparative Medicine, National Human Diseases Animal Model Resource Center, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical C
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause skeletal muscle, myocardial, and gastrointestinal lesions. However, it is currently unclear whether these lesions are caused directly by viral infection or indirectly after infection and whether there are differences between different animal models. Here, we first compared the pathological changes of skeletal muscle, myocardium, and gastrointestinal smooth muscle of different COVID-19 animal models (rhesus monkey, hamster, ferret, hACE2 transgenic mice, hACE2-K18 transgenic mice, mink, and cat), and analyzed the possible mechanism of pathological changes.
View Article and Find Full Text PDFNat Commun
April 2025
Neuroscience Graduate Program, University of Rochester, Rochester, NY, 14642, USA.
Sensory circuits are organized in parallel, e.g. parallel streams relay feedforward visual information from retina to cortex.
View Article and Find Full Text PDFMol Ther Nucleic Acids
September 2024
Feldan Therapeutics, 2666 Boulevard du Parc Technologique Suite 290, Québec, QC G1P 4S6, Canada.
Delivery of antisense oligonucleotides (ASOs) to airway epithelial cells is arduous due to the physiological barriers that protect the lungs and the endosomal entrapment phenomenon, which prevents ASOs from reaching their intracellular targets. Various delivery strategies involving peptide-, lipid-, and polymer-based carriers are being investigated, yet the challenge remains. S10 is a peptide-based delivery agent that enables the intracellular delivery of biomolecules such as GFP, CRISPR-associated nuclease ribonucleoprotein (RNP), base editor RNP, and a fluorescent peptide into lung cells after intranasal or intratracheal administrations to mice, ferrets, and rhesus monkeys.
View Article and Find Full Text PDFVaccines (Basel)
November 2023
Research Institute for Biological Safety Problems, The Ministry of Health of the Republic of Kazakhstan, Gvardeiskiy 080409, Kazakhstan.
Creating an effective and safe vaccine is critical to fighting the coronavirus infection successfully. Several types of COVID-19 vaccines exist, including inactivated, live attenuated, recombinant, synthetic peptide, virus-like particle-based, DNA and mRNA-based, and sub-unit vaccines containing purified immunogenic viral proteins. However, the scale and speed at which COVID-19 is spreading demonstrate a global public demand for an effective prophylaxis that must be supplied more.
View Article and Find Full Text PDFmSphere
October 2023
Departments of Pediatrics & Medicine, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Single-cell RNA-seq has been used to characterize human COVID-19. To determine if preclinical models successfully mimic the cell-intrinsic and -extrinsic effects of severe disease, we conducted a meta-analysis of single-cell data across five model species. To assess whether dissemination of viral RNA in lung cells tracks pathology and results in cell-intrinsic and -extrinsic transcriptomic changes in COVID-19.
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