Construction of a bivalent vaccine candidate against HAdV4/HAdV7 based on capsid-display strategy via Red-homologous recombination and counter-selection methodology  

作　　者：Peng Wang Yunting Shao Xichun Yang Wenning Zhang Jianguang Zhou Fang Huang Shuang Liu Jiping Zheng Chengjun Wu Shanhu Li 

机构地区：[1]Department of Cell Engineering,Beijing Institute of Biotechnology,Beijing 100850,China [2]School of Basic Medical Sciences,Faculty of Medicine,Dalian University of Technology,Dalian 116024,China [3]Lab of Microbiological Engineering,School of Life and Health Sciences,Hainan University,Haikou 570228,China

出　　处：《Biosafety and Health》2024年第2期70-79,共10页生物安全与健康（英文）

基　　金：supported by grants from the National Key Research and Development Program of China(Grant No.2018YFA0900800).

摘　　要：Human adenoviruses(HAdvs)are major respiratory pathogens.Specifically,human adenovirus type 4(HAdV4)and human adenovirus type 7(HAdV7)are known for causing fever and pneumonia,with docu-mented cases of fatalities among the population.In recent years,HAdV4/HAdv7 has been implicated in caus-ing substantial outbreaks,leading to increased morbidity in multiple countries.Most HAdV4 and HAdV7 infections have been reported in North America,Asia,Europe,Africa,South America,Oceania,and the Middle East.Most fatalities occurred in North America(the United States)and Asia(China and Singapore).Engineered recombinant adenoviruses have played a crucial role as vaccine vectors.In this study,we con-structed a recombinant adenovirus,Ad4ITRmut-Ad7E3,and evaluated it in vitro and in vivo.We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain,indicating that the mutation of inverted terminal repeats(ITRs)weakened the replication ability of HAdV4.Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain,administered by intraperitoneal injection and oral gavage,resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdv7.This finding not only pro-vides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vac-cine candidate against HAdV4 and HAdv7 but also against other prevalent adenovirus serotypes such as HAdV3,HAdV11,HAdV14,and HAdv55,from various regions.

关 键 词：Bivalent adenovirus vaccine Capsid-display strategy ITRs modification Hexon epitope replacement 

分 类 号：R186[医药卫生—流行病学]