title: Spatiotemporal hierarchy in antibody recognition against transmitted HIV-1 envelope glycoprotein during natural infection.
abstract: BACKGROUND
  Majority of HIV-1 infection is established by one transmitted/founder virus and understanding how the neutralizing antibodies develop against this virus is critical for our rational design an HIV-1 vaccine.
  
  
  RESULTS
  We report here antibody profiling of sequential plasma samples against transmitted/founder HIV-1 envelope glycoprotein in an epidemiologically linked transmission pair using our previously reported antigen library approach. We have decomposed the antibody recognition into three major subdomains on the envelope and showed their development in vivo followed a spatiotemporal hierarchy: starting with the ectodomain of gp41 at membrane proximal region, then the V3C3V4 and the V1V2 of gp120 at the membrane distal region. While antibodies to these subdomains appeared to undergo avidity maturation, the early anti-gp41 antibodies failed to translate into detectable autologous neutralization. Instead, it was the much delayed anti-V3C3V4 and anti-V1V2 antibodies constituted the major neutralizing activities.
  
  
  CONCLUSIONS
  Our results indicate that the initial antibody response was severely misguided by the transmitted/founder virus and future vaccine design would need to avoid the ectodomain of gp41 and focus on the neutralizing targets in the V3C3V4 and V1V2 subdomains of gp120.
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China. iamjinsu@163.com.
authors.forename: Su
authors.initials: S
authors.lastname: Jin
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, No. 1 Hospital of China Medical University, Shenyang, 110001, China. yangtao790707@gmail.com.
authors.forename: Yangtao
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China. wangqianjiaojiao@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China. wanghua919@gmail.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China. shixuanlingsk@mail.tsinghua.edu.cn.
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, No. 1 Hospital of China Medical University, Shenyang, 110001, China. xxhan@yeah.net.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Han
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. tzhou@mail.nih.gov.
authors.forename: Tongqing
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, No. 1 Hospital of China Medical University, Shenyang, 110001, China. hongshang100@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China. zhanglinqi@tsinghua.edu.cn.
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D015331:Cohort Studies; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D062211:Spatio-Temporal Analysis; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus