One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model.

Autor: Gooch KE; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Smith TRF; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA., Salguero FJ; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Fotheringham SA; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Watson RJ; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Dennis MJ; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Handley A; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Humphries HE; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Longet S; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Tipton T; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Sarfas C; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Sibley L; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Slack GS; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Rayner E; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Ryan KA; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Schultheis K; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA., Ramos SJ; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA., White A; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Charlton S; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Sharpe SA; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Gleeson F; Department of Oncology, Oxford University, Oxford, UK., Humeau LM; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA., Hall Y; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom., Broderick KE; Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA., Carroll MW; Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom; Wellcome Centre for Human Genetics, Nuffield Dept of Medicine, Oxford University, OX3 7BN, UK.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2021 Aug 09; Vol. 39 (34), pp. 4885-4894. Date of Electronic Publication: 2021 Jun 23.
DOI: 10.1016/j.vaccine.2021.06.057
Abstrakt: Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 10 6 pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.
Competing Interests: Declaration of Competing Interest TRFS, LMH, SJR, KS and KEB are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. All other authors report there are no conflicting interests.
(Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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