Differential ChAdOx1 and ChAdOx2 transduction efficiency and receptor specificity in human and mouse B cell lines in vitro

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Adenoviruses represent versatile platforms for vaccine development and gene therapy, owing to their broad tropism and capacity to transduce a wide range of cellular subsets, including antigen-presenting cells such as dendritic cells and B cells. Adenoviral tropism is strongly influenced by serotype and viral origin, which together determine the efficiency with which distinct cellular phenotypes are infected. Among currently used platforms, the replication-incompetent chimpanzee adenoviral vectors ChAdOx1 and ChAdOx2 have gained prominence because of their favourable safety profiles and robust immunogenicity in vaccine applications. However, their cellular tropism, particularly with respect to B cells, remains incompletely characterised. The coxsackievirus and adenovirus receptor (CAR) is the primary entry receptor for many adenoviruses, yet its expression is limited on several immune cell types, including B cells. Here, we demonstrate that both ChAdOx1 and ChAdOx2 efficiently transduce human and murine B cell lines, albeit at low levels. Receptor-blocking experiments indicate that both vectors utilise CAR in conjunction with alternative receptors, including CD86 and integrins. Notably, ChAdOx1, but not ChAdOx2, additionally exploits CD46 for B cell line transduction. These latter experimental findings were further supported by complementary molecular docking analyses. Overall, ChAdOx1 displayed higher transduction efficiency in the human B cell lines examined, whereas ChAdOx2 showed preferential tropism for the murine B cell line BAL17. Together, these results provide new insights into the receptor-mediated entry mechanisms of ChAdOx1 and ChAdOx2 and highlight distinct receptor usage and species-specific differences in B cell line tropism.

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