Vaccines based on replication incompetent Ad26 viral vectors: Standardized template with key considerations for a risk/benefit assessment
Vaccine, vol. 39, pp. 3081–3101
Abstract
Replication-incompetent adenoviral vectors have been under investigation as a platform to carry a variety of transgenes, and express them as a basis for vaccine development. A replication-incompetent adenoviral vector based on human adenovirus type 26 (Ad26) has been evaluated in several clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and features of recombinant viral vector vaccines. This paper reviews features of the Ad26 vectors, including tabulation of safety and risk assessment characteristics of Ad26-based vaccines. In the Ad26 vector, deletion of E1 gene rendering the vector replication incompetent is combined with additional genetic engineering for vaccine manufacturability and transgene expression optimization. These vaccines can be manufactured in mammalian cell lines at scale providing an effective, flexible system for high-yield manufacturing. Ad26 vector vaccines have favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the Ad26 vaccine safety database version 4.0, with unblinded data from 23 ongoing and completed clinical studies for 3912 participants in five different Ad26-based vaccine programs. Overall, Ad26-based vaccines have been well tolerated, with no significant safety issues identified. Evaluation of Ad26-based vaccines is continuing, with >114,000 participants vaccinated as of 4th September 2020. Extensive evaluation of immunogenicity in humans shows strong, durable humoral and cellular immune responses. Clinical trials have not revealed impact of pre-existing immunity to Ad26 on vaccine immunogenicity, even in the presence of Ad26 neutralizing antibody titers or Ad26-targeting T cell responses at baseline. The first Ad26-based vaccine, against Ebola virus, received marketing authorization from EC on 1st July 2020, as part of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen. New developments based on Ad26 vectors are underway, including a COVID-19 vaccine, which is currently in phase 3 of clinical evaluation.
Authors 16
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Affiliation as printed
Janssen Vaccines & Prevention, Leiden, the Netherlands
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Affiliation as printed
Janssen Research & Development, Titusville, NJ, USA
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Affiliation as printed
Janssen Vaccines & Prevention, Leiden, the Netherlands
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The Task Force for Global Health
Affiliation as printed
Brighton Collaboration, A Program of the Task Force for Global Health, Decatur, GA, USA
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Affiliation as printed
Janssen Research & Development, Titusville, NJ, USA
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Affiliation as printed
Independent Adviser, United Kingdom
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Affiliation as printed
Janssen Vaccines & Prevention, Leiden, the Netherlands
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Affiliation as printed
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA
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Affiliation as printed
Janssen Vaccines & Prevention, Leiden, the Netherlands
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Affiliation as printed
Janssen Pharmaceutica NV, Beerse, Belgium
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Affiliation as printed
Janssen Vaccines & Prevention, Leiden, the Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention, Leiden, the Netherlands
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Affiliation as printed
Janssen Vaccines & Prevention, Leiden, the Netherlands
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The Task Force for Global Health
Affiliation as printed
Brighton Collaboration, A Program of the Task Force for Global Health, Decatur, GA, USA
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The Task Force for Global Health
Affiliation as printed
Brighton Collaboration, A Program of the Task Force for Global Health, Decatur, GA, USA
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The Task Force for Global Health
Affiliation as printed
Brighton Collaboration, A Program of the Task Force for Global Health, Decatur, GA, USA
Cited by 83 stored of 84
Cited by patents worldwide 2 (Lens.org)
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STABILIZED TRIMERIC CLASS I FUSION PROTEINSWO2024061753A1 2024-03-28 Pending
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SEQUENTIAL ADMINISTRATION OF ADENOVIRUSESWO2023198815A1 2023-10-19 Pending