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Adenovirus serotype 26 (Ad26) entry receptors are a group of host cell surface molecules that facilitate the attachment and internalization of the Ad26 virus, a member of the species D human adenoviruses. Unlike the more common Ad5, which primarily uses the coxsackievirus and adenovirus receptor (CAR), Ad26 utilizes a dual-receptor system involving CD46 (membrane cofactor protein) and sialic acid-bearing glycans for initial docking. Recent evidence suggests that the viral hexon protein interacts with CD46, while the fiber knob binds to sialic acid, allowing the virus to infect a wide range of cell types, including those with low CAR expression. Following attachment, the virus engages secondary receptors, specifically alpha-v beta-3 and alpha-v beta-5 integrins, which trigger clathrin-mediated endocytosis to deliver the viral genome to the host cell nucleus. These receptors are of critical importance in biotechnology as Ad26 is a leading platform for viral vector vaccines, such as the Janssen COVID-19 vaccine and the Zabdeno Ebola vaccine. The distribution and density of these receptors on host cells determine the vaccine's tropism and the efficiency of transgene expression, while their interaction with the viral capsid is also a focus of research into rare adverse events like vaccine-induced immune thrombotic thrombocytopenia (VITT).
Viral vector-mediated delivery of genetic material for antigen expression via receptor-mediated endocytosis
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