iScience · 2025
Novel adenovirus vaccine vectors lacking thrombosis-associated interactions with platelet factor 4.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sallard Erwan, Pembaur Daniel, Ciancaglini Matias, Manov-Bouard Lucie, Weklak Denice, Hamdan Firas, Chan Chun Kit, Jönsson Franziska, Chabot Elise, Musielak Carmen, Scurti Elena, Feola Sara, Schellhorn Sebastian, Beaude Nissai, Schröer Katrin, Sarkar Daipayan, Koukou Georgia, Wang Xiaoyan, Schmidt Natascha, Bayer Wibke, Aydin Malik, Kemp Vera, Parker Alan L, Grimm Dirk, Viitala Tapani, Cerullo Vincenzo, Singharoy Abhishek, Baker Alexander T, Zhang Wenli, Pinschewer Daniel, Kreppel Florian, Ehrhardt Anja
Аннотация
The adenoviral vector-based AstraZeneca and Janssen COVID-19 vaccines have been associated with rare cases of thrombosis, believed to be triggered, among other factors, by vector binding to the blood protein platelet factor 4 (PF4). To identify vectors with lower thrombosis risk, we screened 50 natural and hexon-modified adenoviruses (Ads). Unlike the applied COVID-19 vaccines and most tested vectors, Ad34 and Ad80, as well as Ad5 vectors with deleted or chemically shielded hexon hyper-variable region 1 (HVR1), did not bind to PF4. Furthermore, interactions with PF4 substantially modified Ad5 infectivity in various immortalized and primary cells, suggesting that PF4 may influence existing vector tropism. Finally, HVR1-deleted Ad5 and Ad34 vectors expressing SARS-CoV-2 spike S1 domain were tested as vaccine candidates in mice and induced robust cellular immune responses. Therefore, the identified PF4 non-binding vectors may represent safe and efficient candidates for clinical applications.