title: Simian immunodeficiency virus infection evades vaccine-elicited antibody responses to V2 region.
abstract: OBJECTIVE
  An effective AIDS vaccine should elicit protective antibody responses against HIV/simian immunodeficiency virus (SIV) infection. We recently reported that mucosal priming with a replicating modified vaccinia Tiantan virus (MVTTgpe)-based vaccine regimen induces durable protection against pathogenic SIVmac239 infection in rhesus monkeys. Here, we aim to conduct a comprehensive analysis on antigenic determinants recognized by specific antibody responses generated by vaccination and SIVmac239 infection.
  
  
  METHODS
  A novel yeast surface displayed antigen library of entire SIVmac239 envelope (Env) glycoprotein was established and validated to map the major antigenic determinants (MAD) in monkey sera elicited by vaccination and infection. MAD-directed antibody responses were further analyzed for correlation of protection.
  
  
  CONCLUSIONS
  The yeast surface displayed library allows the mapping of SIV-specific linear and conformational MAD. The MVTTgpe-based regimen induces antibodies targeting mainly to 6 antigenic domains covering the entire gp160. Critically, this regimen induced a uniquely predominant antibody response against a distinct MAD in variable region 2 (V2) as compared with the Ad5gpe-based vaccine and SIVmac239 infection. This MAD was associated with a higher titer of anti-V2 antibody responses, which was inversely correlated with peak and set-point viral loads. Unexpectedly, the pathogenic SIVmac239 challenge evaded the vaccine-elicited anti-V2 antibody response. Instead of recalling B-cell memory responses to the V2 MAD, viral infection directed anti-V1V2 antibodies primarily to V1 region. Moreover, the anti-V1V2 antibody responses diminished significantly in infected macaques after they enter the stage of simian AIDS. Our findings have critical implications to AIDS vaccine efforts with focus on V2 region.
authors.affiliation: *AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, Research Center for Infection and Immunity, The University of Hong Kong, Hong Kong, China; †Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, China; and §State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Xilin
authors.initials: X
authors.lastname: Wu
authors.forename: Jiansong
authors.initials: J
authors.lastname: Tang
authors.forename: Caijun
authors.initials: C
authors.lastname: Sun
authors.forename: Liqiang
authors.initials: L
authors.lastname: Feng
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D057131:Immune Evasion; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins