Manufacturing a chimpanzee adenovirus‐vectored SARS‐CoV‐2 vaccine to meet global needs

Abstract

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing"

Safety and immunogenicity of a simian-adenovirus-vectored rabies vaccine: an open-label, non-randomised, dose-escalation, first-in-human, single-centre, phase 1 clinical trial

“…As well as adenovirus-vectored vaccines' clinical track record of safety, immunogenicity, and efficacy, the platform offers low manufacturing costs and stability suitable for straightforward distribution in rabies-endemic countries. 10,33 In addition to the liquid formulations used with current licensed rabies vaccines, which permit storage at 2-8°C, we showed stability of ChAdOx2 RabG for 1 year at 20°C in a first-generation lyophilised formulation. 34 The safety and immunogenicity of ChAdOx2 RabG are now being evaluated in a phase 1b-2 study in Tanzania.…”

“…8 The ChAdOx2 vector is based on a different adenovirus serotype from the ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria, Oxford/AstraZeneca) but can be produced with the same low-cost manufacturing process. 9,10 Our main goal in developing this product is to enable low-cost single-visit PrEP to be included in routine vaccination schedules in rabies-endemic areas. We have completed a phase 1 clinical trial to investigate the safety and immunogenicity of ChAdOx2 RabG in healthy UK adults.…”

Process- and product-related impurities in the ChAdOx1 nCov-19 vaccine

“…Compared to the manufacturer’s batch-release data the difference between actual and assumed HCP content, respectively, was even several hundred-fold in some of the lots. The substantial lot-to-lot variation in HCP content in a total of four tested samples ( Figure 1 and Table 1 ) also indicated a lack of robustness of the process used for purification of the vaccine, a process, which recently has been described in detail ( Joe et al, 2022 ). In contrast, in three tested lots of the Ad26.COV2.S vaccine, contamination with HCPs was negligible, confirming that excellent purification of clinical grade adenovirus vaccines is possible at an industrial scale.…”

“…Previously, it has been shown, that simian adenovirus vectors including ChAdOx1 can be purified at high yield and purity using such technology for purification ( Fedosyuk et al, 2019 ). To meet global needs and to enable commercial manufacturing of clinical grade material at a very large scale, some modifications and simplifications, respectively, had been introduced both into the upstream and downstream processes, as has been described in detail ( Joe et al, 2022 ). Although in our experiment the same number of viral particles was loaded, the staining pattern of ChAdOx1 looked very different, when compared to the adenoviral vector control ( Figure 1 ).…”

Pandemic-response adenoviral vector and RNA vaccine manufacturing

“…For saRNA vaccines the DS amount per dose was obtained from the clinical trial registry 84 . Information on AVV vaccine production was obtained from the scientific literature [85][86][87][88] . The AVV vaccine production process was modelled based on the manufacturing of the replication-deficient chimpanzee adenovirus-vectored (ChAdOx1) vaccine which was co-developed by Oxford University and AstraZeneca plc.…”