Risk assessment of the Sputnik V vaccine

rAd5-S-CoV2 and rAd26-S-CoV2 are replication-defective, recombinant adenoviruses of serotypes 5 and 26, respectively, which are used as components of a vaccine against SARS-CoV-2. Adenovirus 5 (Ad5) is taxonomically assigned to the species human mastadenovirus C, while adenovirus 26 (Ad26) belongs to the species human mastadenovirus D. Representatives of both species are associated with mild human disease and, as donor and recipient organisms for genetic engineering, are classified in risk group 2. In both vaccine viruses, the E1 and E3 gene regions have been deleted from their genomes, with the absence of the E1 gene region causing the replication defect in the viral genomes. Furthermore, in the rAd26-S-CoV2 virus, parts of the E4 gene region have been replaced with the homologous nucleic acid segment of Ad5. Finally, a gene responsible for the complete Spike protein (S) of SARS-CoV-2 coding nucleic acid segment is inserted. Expression of the S protein is under the control of the cytomegalovirus promoter. To produce rAd5-S-CoV2 and rAd26-S-CoV2 particles, the human cell line HEK293 used, whose genome contains part of the Ad5 genome, including the E1 gene region. The restoration of replication competence during the production process of rAd5-S-CoV2 in HEK293 cells cannot therefore be ruled out due to possible recombination events. Numerous results from clinical studies are already available on the biological safety of rAd5-S-CoV2 and rAd26-S-CoV2. The side effects of vaccinations with the recombinant viruses were predominantly mild and, in a few cases, moderate. The combination vaccine with rAd5-S-CoV2 and rAd26-S-CoV2 has now been approved in more than 60 countries. Here, too, the side effects of the vaccination were predominantly mild to moderate. In very rare cases, severe or very severe side effects occurred after vaccination. Due to the similarity to previously evaluated vaccines (see also ZKBS Statement Ref. No. 45242.0180, July 2020), the results from clinical trials, and the experience from vaccination campaigns, the ZKBS classifies the recombinant, replication-defective adenoviruses rAd5-S-CoV2 and rAd26-S-CoV2 as genetically modified organisms in accordance with Section 5 Paragraph 1 GenTSV in conjunction with the criteria in Annex 1 GenTSV in risk group 1. However, it should be noted that due to the possibility of homologous recombination and the associated elimination of the replication defect in the production of rAd5-S-CoV2 particles in HEK293 cells, this constitutes genetic engineering work of safety level 2. The rAd5-S-CoV2 particles can only be handled under safety level 1 conditions once it has been demonstrated that no replication-competent adenoviruses are present (taking into account the detection limit permitted by European production standards for medicinal products).

The ZKBS statement can be found at File number 45242.0193 can be retrieved.