Exploration of a Sequential Gp140-Gp145 Immunization Regimen with Heterologous Envs to Induce a Protective Cross-Reactive HIV Neutralizing Antibody Response In Non-human Primates  

作　　者：Xiangqing Ding Kangli Cao Jing Wang Yanmin Wan Qinyun Chen Yanqin Ren Yongtang Zheng Mingzhao Zhu Renrong Tian Wenjun Wang Chen Zhao Xiaoyan Zhang Jianqing Xu 

机构地区：[1]Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences,Key Laboratory of Medical Molecular Virology,Shanghai Medical College,Fudan University,Shanghai 201508,China [2]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China [3]University of Chinese Academy of Sciences,Beijing 100049,China [4]Key Laboratory of Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [5]College of Life Sciences,University of the Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Virologica Sinica》2021年第4期784-795,共12页中国病毒学（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81672018,81561128008);the National Basic Research Program of China(973program#2014CB542502);the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102);Shanghai Pujiang Program(19PJ1409100);Intramural Funding from Shanghai Public Health Clinical Center.

摘　　要：Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.

关 键 词：Human immunodeficiency virus type 1(HIV-1) Vaccine Broadly neutralizing antibodies(bnAbs) Sequential immunization Native-like Env trimers Nanoparticle 

分 类 号：R392[医药卫生—免疫学]