Vaccines have relieved the public health burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and globally inactivated vaccines are most widely used. However, poor vaccination accessibility and waning immunity maintain the pandemic, driving emergence of variants. We developed an inactivated SARS-CoV-2 (I-SARS-CoV-2) vaccine based on a viral isolate with the Spike mutation D614G, produced in Vero cells in a scalable bioreactor, inactivated with β-propiolactone, purified by membrane-based steric exclusion chromatography, and adjuvanted with MF59-like adjuvant AddaVax. I-SARS-CoV-2 and a derived split vaccine induced persisting neutralising antibodies in mice; moreover, lyophilised antigen was immunogenic. Upon homologous challenge, I-SARS-CoV-2 immunised hamsters were protected against disease and lung pathology. In contrast to reports for widely used vaccines, hamster plasma similarly neutralised the homologous and the Delta (B.1.617.2) variant viruses, while the Omicron (B.1.1.529) variant was neutralised less efficiently. Applied bioprocessing approaches offer advantages regarding scalability and production, potentially benefitting worldwide vaccine coverage.