Human adenovirus type 26 entry receptors (Ad26 receptors)

Human adenovirus type 26 (Ad26) entry receptors are a group of host cell surface molecules that facilitate the attachment and internalization of Ad26-based viral vectors, which are utilized in major vaccine platforms such as the Janssen COVID-19 vaccine (Ad26.COV2.S) and the Ebola vaccine (Ad26.ZEBOV). The primary receptors for Ad26 include CD46 (Membrane Cofactor Protein), which interacts with the viral hexon protein, and sialic acid-bearing glycans, which bind to the fiber knob. Unlike the common Ad5 vector that primarily uses the Coxsackievirus and Adenovirus Receptor (CAR), Ad26 utilizes these alternative receptors to achieve a distinct tissue tropism and to bypass pre-existing anti-Ad5 immunity. Secondary interactions with cellular integrins, such as alpha-V beta-3 and alpha-V beta-5, via the penton base RGD motif are also involved in the endocytic process. Understanding these receptor interactions is critical for optimizing the delivery of genetic payloads and for assessing safety concerns, including the rare but serious Thrombosis with Thrombocytopenia Syndrome (TTS) associated with adenoviral vector vaccines. This receptor profile allows Ad26 to infect a broad range of cell types, including dendritic cells and epithelial cells, making it a potent tool for inducing both humoral and cellular immune responses.

Other names

CD46Membrane cofactor proteinMCPSialic acid-bearing glycansCoxsackievirus and adenovirus receptor (CAR)Integrin alpha-V beta-3Integrin alpha-V beta-5SR-A6MARCO

Viral vector attachment to host cell receptors (CD46 and sialic acid) followed by integrin-mediated endocytosis and nuclear delivery of the transgene for expression of the encoded antigen.