title: HIV-1 vaccines based on replication-competent Tiantan vaccinia protected Chinese rhesus macaques from simian HIV infection.
abstract: OBJECTIVE
  To assess the efficacy of HIV vaccines constructed from replication-competent Tiantan vaccinia virus (rTV) alone or combined with DNA in protecting Chinese rhesus macaques from homologous Simian/Human Immunodeficiency Virus (SHIV)-CN97001 challenge.
  
  
  METHODS
  The nef, gag, pol, and gp140 genes from strain CRF07_BC HIV-1 CN54 were selected to construct an HIV vaccine using the rTV or rTV/DNA vaccine. After vaccination, the vaccine and control groups were intravenously challenged with SHIV-CN97001 (32 MID50). HIV-specific antibodies and neutralizing antibodies, gp70 V1V2 binding antibodies, and cytotoxic T-lymphocyte responses were measured prospectively after vaccination with an ELISA, a virus infectivity assay in TZM-bl cells, and ELISPOT assays, respectively. Viral RNA was quantified after challenge with real-time reverse transcriptase-PCR (RT-PCR), and protection efficacy was determined with an analysis of CD8 lymphocyte depletion in vivo.
  
  
  RESULTS
  Both rTV and DNA/rTV vaccine groups developed strong cellular and humoral responses against HIV-1 CN54 antigens, including Gag and Env, and also developed significant and persistent anti-Env antibodies and neutralizing antibodies after immunization. Both the rTV and DNA/rTV groups were significantly protected against SHIV-CN97001 or displayed lower viremia than the controls. After CD8 lymphocyte depletion, no viremia was detectable in the vaccinated monkeys, but rebounded rapidly in the control animals. Protection against infection correlated with vaccine-elicited neutralizing antibodies specific for homologous HIV-1 viruses.
  
  
  CONCLUSIONS
  An rTV-based HIV-1 vaccine, with or without a DNA primer, provided protection from SHIV challenge in a macaque model. Replication-competent Tiantan vaccinia is a promising vector and should enable advances in HIV-1 vaccine development.
authors: aState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention bNational Institutes for Food and Drug Control, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Beijing cCollege of Life Science, Nankai University, Tianjin dInstitute of Medical Biology, CAMS, Kunming eInstitute of Laboratory Animal Sciences, CAMS, Beijing fCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. *Drs Qiang Liu, Yue Li and Zhenwu Luo contributed equally to the writing of this article.
authors: Qiang
authors: Q
authors: Liu
authors: Yue
authors: Y
authors: Li
authors: Zhenwu
authors: Z
authors: Luo
authors: Guibo
authors: G
authors: Yang
authors: Yong
authors: Y
authors: Liu
authors: Ying
authors: Y
authors: Liu
authors: Maosheng
authors: M
authors: Sun
authors: Jiejie
authors: J
authors: Dai
authors: Qihan
authors: Q
authors: Li
authors: Chuan
authors: C
authors: Qin
authors: Yiming
authors: Y
authors: Shao
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D004195:Disease Models, Animal; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*; D014766:Viremia / Q000517:prevention & control
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D004337:Drug Carriers; D015483:HIV Antibodies; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic