Novel adenovirus vaccine vectors lacking thrombosis-associated interactions with platelet factor 4

TL;DR

Researchers identified safer adenovirus-based vaccine vectors that do not bind to a blood protein linked to rare cases of thrombosis.

Contribution

Development of adenovirus vectors lacking interactions with platelet factor 4 (PF4), reducing thrombosis risk.

Findings

Ad5-ΔHVR1, Ad34, and Ad80 adenoviruses do not bind to PF4.

Ad5-ΔHVR1 was as effective as Ad5 in inducing immune responses in mice.

PF4 binding influences the infectivity of adenoviruses.

Abstract

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.

•We developed higher-throughput methods to study adenovirus binding to PF4•Ad5-ΔHVR1, Ad34, and Ad80 do not bind to PF4•Ad5-ΔHVR1 was non-inferior to Ad5 as a vaccine vector in mice•PF4 modified the infectivity of adenoviruses that bind PF4

We developed higher-throughput methods to study adenovirus binding to PF4

Ad5-ΔHVR1, Ad34, and Ad80 do not bind to PF4

Ad5-ΔHVR1 was non-inferior to Ad5 as a vaccine vector in mice

PF4 modified the infectivity of adenoviruses that bind PF4

Molecular biology; Immune response

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