Risk assessment of recombinant vaccine viruses

The four recombinant vaccine viruses Ad26.Mos2S.Env, Ad26.Mos1.Env, Ad26.Mos1.gag-pol and Ad26.Mos2.gag-pol and the recombinant vaccine virus Ad26.RSV.preF are based on the adenovirus (Ad) 26, which was first isolated from an anal swab of a nine-month-old boy in 1956. Ad26 belongs to the *species Human mastadenovirus *D, which has been relatively little studied to date. However, gastrointestinal and conjunctival infections are attributed to Ad26, and the viruses are therefore classified as Risk group 2 The Ad26-based vector underlying all five viruses is replication-defective on non-complementing cells due to the deletion of the E1 gene region. Furthermore, the E3 gene region, which encodes immunomodulatory factors, was deleted. Furthermore, the open reading frame 6 (ORF6) of the E4 region was replaced with the homologous region from adenovirus 5 (Ad5). A synthetically produced nucleic acid segment was inserted into the E1 region under the control of the cytomegalovirus promoter and the SV40 poly(A) signal to obtain the recombinant vaccine viruses. To produce the Ad26-based viruses, a recombinant cell line is used that provides the E1 gene region of Ad5 required for replication, contains a TetR element, and, due to a lack of homology, does not allow homologous recombination to form replication-competent viruses. The vaccine viruses Ad26.Mos2S.Env, Ad26.Mos1.Env, Ad26.Mos1.gag-pol and Ad26.Mos2.gag-pol contain different nucleic acid segments of the human immunodeficiency virus 1 (HIV-1) and are components of the potential vaccine Ad26.Mos4.HIV, which is directed against HIV-1. Ad26.RSV.preF contains the gene for the F protein of the respiratory syncytial virus (RSV, species human orthopneumovirus, strain A2 in the prefusion conformation (preF)) and is intended for future use as a vaccine against RSV infections of the respiratory tract. Data on Ad26-based vaccines are already available from numerous clinical trials. Vaccines based on the Ad26 vector backbone have also already been approved. Ad26.COVS, which contains the gene for the spike protein of the severe acute respiratory syndrome-related coronavirus virus (SARS-CoV-2) and is already approved as a vaccine, was recently assigned to risk group 1 by the ZKBS (ref. 45242.0180). Data are now available from initial clinical trials in which the potential vaccine Ad26.Mos.HIV was used in a heterologous vaccination strategy. Adverse events such as pain at the injection site, muscle pain, fatigue, and headache were observed, but these disappeared after a few days. Study data are also available for Ad26.RSV.preF, in which mild to moderate transient adverse events were observed after vaccination. The ZKBS classifies Ad26.Mos2S.Env, Ad26.Mos1.Env, Ad26.Mos1.gag-pol, Ad26.Mos2.gag-pol, and Ad26.RSV.preF in accordance with Section 5 Paragraph 1 of the GenTSV in conjunction with the criteria in Annex 1 of the GenTSV as Risk group 1 because these replication-defective viruses carry nucleic acid fragments of HIV-1 or RSV without any potential risk. Furthermore, recombinant viruses with the Ad26 vector backbone are already approved as medicinal products in the EU and have been well tolerated in clinical trials.

The ZKBS statement can be found at File number 45242.0188 can be retrieved.