Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

We develop candidate HIV-1 vaccines, of which two components, ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62), are delivered by the simian adenovirus-derived vaccine vector ChAdOx1. Aberrant adenovirus RNA splicing involving transgene(s) coding for SARS-CoV-2 spike was suggested as an aetiology rare adverse events temporarily associated with initial deployment adenovirus-vectored vaccines during COVID-19 pandemic. Here, to eliminate this theoretically plausible phenomenon from list possible pathomechanisms our candidates, we directly sequenced mRNAs in C1- C62-infected nonpermissive MRC-5 A549 permissive HEK293 human cell lines. Our main observations cells, most similar those become infected after intramuscular administration into volunteers, were that (i) dominant vector-derived expected transcripts HIVconsvX immunogens (ii) atypical within synthetic open reading frame transgenes rare. conclude inadvertent is not a safety concern tested vaccines.