【美开发出实验性猿类免疫缺陷病毒疫苗】

男丁格尔

【美开发出实验性猿类免疫缺陷病毒疫苗】美国研究人员报告，他们开发出一种实验性猿类免疫缺陷病毒疫苗，可大幅降低恒河猴感染猿类艾滋病病毒的风险。与注射安慰剂恒河猴相比，注射实验性疫苗恒河猴感染猿类免疫缺陷病毒风险低80％。该研究成果为开发人类艾滋病疫苗提供了新思路

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeysPreclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges1, 2, 3. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIVSME543 Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection4, 5 against repetitive, intrarectal SIVMAC251 challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.

Figures at a glanceleft

• Figure 1: Immunogenicity and protective efficacy of the adenovirus/poxvirus vaccines.
  
                                 
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  a, Cellular immune responses to SIVSME543 and SIVMAC239 Gag, Pol and Env as determined by IFN-γ ELISPOT assays at weeks 0, 10, 24, 26, and 52. PBMC, peripheral blood mononuclear cells; SFC, spot-forming cells. b, CD8+ and CD4+ total, central/transitional memory (CM; CD28+CD95+), and effector memory (EM; CD28−CD95+) responses to Gag, Pol and Env as determined by multiparameter IFN-γ ICS assays at week 26. c, SIVMAC251 Env ELISAs at weeks 0, 10, 24, 28, and 52. d, SIVSME660 and SIVMAC251 tier 1 pseudovirus NAb assays at weeks 0, 28, and 52. Error bars represent s.e.m. e, Number of challenges required for acquisition of infection in each vaccine group. f, Statistical analyses include the number of challenges required for 50% infection, hazard ratios with 95% confidence intervals (CI), per-exposure vaccine efficacy and per-exposure risks of infection in each group. P-values reflect Wald tests using a proportional hazard model. g, Log SIV RNA copies per ml are depicted for each vaccine group at viral set point (day 84). **P = 0.0037, Wilcoxon rank-sum tests. The horizontal lines represent mean set point log viral loads. Ad, adenovirus; D, DNA; M, MVA.
  
  
• Figure 2: Correlates of protection against acquisition of infection and virological control with the adenovirus/poxvirus vaccines.
  
                                 
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  a, b, Correlation of log ELISA titres immediately before challenge (a) and log tier 1 NAb titres immediately before challenge (b) with the number of challenges required to establish infection. c, d, Correlation of Gag ELISPOT breadth before challenge (c) and Gag ELISPOT magnitude before challenge (d) with set point viral loads following challenge. Correlates analyses included the 32 vaccinated monkeys (a, b) or the 29 vaccinated animals that became infected (c, d) and did not include the sham controls. P-values reflect Spearman rank-correlation tests. e, V2-specific binding antibodies assessed by surface plasmon resonance response units (RU) for each vaccine group at week 30. *P = 0.002, **P = 0.0007, Wilcoxon rank-sum tests. The horizontal lines represent mean responses. f, Correlation of V2-specific antibody responses with the number of challenges required to establish infection.
  
  
• Figure 3: Immunogenicity and protective efficacy of the adenovirus/adenovirus vaccines.
  
                                 
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  a, Cellular immune responses to SIVSME543 and SIVMAC239 Gag, Pol and Env as determined by IFN-γ ELISPOT assays at weeks 0, 4, 24, 28 and 52. b, CD8+ and CD4+ total, central/transitional memory (CM; CD28+CD95+), and effector memory (EM; CD28&#8722;CD95+) responses to Gag, Pol and Env as determined by multiparameter IFN-γ ICS assays at week 28. c, SIVMAC251 Env ELISAs at weeks 0, 4, 24, 28 and 52. d, SIVSME660 and SIVMAC251 tier 1 pseudovirus NAb assays at weeks 0, 28 and 52. Error bars represent s.e.m. e, Number of challenges required for acquisition of infection in each vaccine group. f, Statistical analyses include the number of challenges required for 50% infection, hazard ratios with 95% confidence intervals (CI), per-exposure vaccine efficacy, and per-exposure risks of infection in each group. P-values reflect Wald tests using a proportional hazard model. g, Log SIV RNA copies per ml are depicted for each vaccine group at viral set point (day 84). **P&#8201;<&#8201;0.001, Wilcoxon rank-sum tests. The horizontal lines reflect mean set point log viral loads.
  
  
• Figure 4: Correlates of protection against acquisition of infection with the adenovirus/adenovirus vaccines.
  

• Dan H. Barouch,1, 2
• Jinyan Liu,1
• Hualin Li,1
• Lori F. Maxfield,1
• Peter Abbink,1
• Diana M. Lynch,1
• M. Justin Iampietro,1
• Adam SanMiguel,1
• Michael S. Seaman,1
• Guido Ferrari,3
• Donald N. Forthal,4
• Ilnour Ourmanov,5
• Vanessa M. Hirsch,5
• Angela Carville,6
• Keith G. Mansfield,6
• Donald Stablein,7
• Maria G. Pau,8
• Hanneke Schuitemaker,8
• Jerald C. Sadoff,8
• Erik M. Billings,9
• Mangala Rao,9
• Merlin L. Robb,9
• Jerome H. Kim,9
• Mary A. Marovich,9
• Jaap Goudsmit8, 10
• & Nelson L. Michael9, 10
• et al.
  

• Affiliations
• Contributions
• Corresponding author
  

Journal name:NatureYear published:(2012)DOI:doi:10.1038/nature10766Received29 September 2011Accepted07 December 2011Published online04 January 2012