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Review
. 2021 May 21;39(22):3081-3101.
doi: 10.1016/j.vaccine.2020.09.018. Epub 2020 Oct 3.

Vaccines based on replication incompetent Ad26 viral vectors: Standardized template with key considerations for a risk/benefit assessment

Jerome Custers  1 , Denny Kim  2 , Maarten Leyssen  1 , Marc Gurwith  3 , Frank Tomaka  2 , James Robertson  4 , Esther Heijnen  1 , Richard Condit  5 , Georgi Shukarev  1 , Dirk Heerwegh  6 , Roy van Heesbeen  1 , Hanneke Schuitemaker  1 , Macaya Douoguih  1 , Eric Evans  3 , Emily R Smith  3 , Robert T Chen  3 ; Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG)
Affiliations
Review

Vaccines based on replication incompetent Ad26 viral vectors: Standardized template with key considerations for a risk/benefit assessment

Jerome Custers et al. Vaccine. .

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.

Keywords: Benefit/risk; Replication-incompetent Ad26; Safety; Vaccine; Viral vector.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Brighton Collaboration V3SWG authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Jerome Custers, Maarten Leyssen, Frank Tomaka, Esther Heijnen, Georgi Shukarev, Dirk Heerwegh, Roy van Heesbeen, Hanneke Schuitemaker, and Macaya Douoguih, are current employees of Janssen Pharmaceuticals and potentially hold stock in J&J.

Figures

Fig. 1
Fig. 1
Summary of number of Ad26-based vaccines administered (full experience and AdVac Safety Database).
See this image and copyright information in PMC

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