Lung-Targeted Transgene Expression of Nanocomplexed Ad5 Enhances Immune Response in the Presence of Preexisting Immunity  

作　　者：Yilong Yang Shipo Wu Yudong Wang Fangze Shao Peng Lv Ruihua Li Xiaofan Zhao Jun Zhang Xiaopeng Zhang Jianmin Li Lihua Hou Junjie Xu Wei Chen 

机构地区：[1]Beijing Institute of Biotechnology,Beijing 100071,China

出　　处：《Engineering》2023年第8期127-139,共13页工程（英文）

基　　金：supported in part by the grant from National Natural Science Foundation of China(82171818,81703048,82041019,and 82101919);the grant from Defense Industrial Technology Development Program of China(JCKY2020802B001);Beijing Municipal Science and Technology Commission(Z201100005420024)。

摘　　要：Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

关 键 词：Adenovirus serotype 5 VACCINE Preexisting immunity Nanoparticles Transgene expression 

分 类 号：R392[医药卫生—免疫学]