ANIMAL MODELS TO DESIGN AND EVALUATE IMPROVED VZV VACCINES

用于设计和评估改进的 VZV 疫苗的动物模型

• 批准号: 7958612
• 负责人: VICKI L TRAINA-DORGE
• 金额: $ 6.04万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958612
• 关键词: Animal Model; Animals; Antigens; Chickenpox; Computer Retrieval of Information on Scientific Projects Database; Control Animal; Control Groups; Funding; Grant; Immune response; Immunization; Institution; Macaca mulatta; Nature; Primates; Production; Recombinants; Research; Research Personnel; Resources; SIV; Simian Acquired Immunodeficiency Syndrome; Source; Testing; United States National Institutes of Health; VZV vaccine; Vaccinated; Vaccines; Viral; Viral Antigens; Viral Load result; Viral load measurement; Viremia; Virus; design; improved; neutralizing antibody; research study; response; subcutaneous

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An SVV recombinant expressing simian immunodeficiency virus (SIV) antigens was used to vaccinate rhesus macaques in a vaccine/challenge experiment. Ten rhesus monkeys, divided into two groups of five animals each, received subcutaneous and intratracheal inoculations/immunizations with SVV-SIVgag and -SIVenv (Grp1) or SVV-RSVG and -RSVM2 (Gp2) at d0 and at 6weeks. Six months after immunization, all animals were intravenously challenged with 100 TCID50 SIVmac251. Virus loads, were reduced in SVV-SIV vaccinated animals compared with SVV-RSV vaccinated animals at d14 post challenge and continued to increase in significance through 258 days following challenge. Mann Whitney analysis showed significantly lower mean viral loads in Grp1 compared with Gp2 at d14 peak viremia: log 6.8 +/-0.2 and log 7.5 +/-0.4 (p=0.016); and d56 viral set point: log5.3+/-0.5 and log and log6.3+/-0.7 (p=0.03), respectively. Humoral and cellular responses to SIV antigens were documented in this vaccinated group versus the control group. Most intriguing was the production of neutralizing antibodies in the vaccinated animals compared with control animals when tested against H9 grown SIVmac251 but not SIVmac239. We are making efforts to molecularly clone SIVmac251-CX-1 pseudotyped viruses to explain the nature of the neutralization. These results demonstrate that recombinant varicella/SIV vaccines can stimulate humoral, cellular, and neutralizing immune responses against SIVmac antigens in the rhesus macaque and suggest the potential of this SVV-SIV recombinant for protection against simian acquired immunodeficiency syndrome.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在疫苗/挑战实验中，使用表达猿猴免疫缺陷病毒（SIV）抗原的SVV重组型抗原接种恒河猴。十只恒河猴分为两组五只动物，接受了svv -sivgag和-sivenv（GRP1）或SVV -RSVG和-RSVG和-RSVM2（GP2）（GP2）（GP2）（GP2）（GP2）（GP2）（GP2）（GP2）的皮下和气管内接种/免疫接种/免疫。免疫接种六个月后，所有动物都用100 TCID50 SIVMAC251静脉注射挑战。 与SVV-RSV接种疫苗接种的动物相比，在挑战后D14接种疫苗的动物相比，SVV-SIV疫苗接种动物的病毒负荷降低，并在挑战后的258天之前继续增加显着性。曼恩·惠特尼（Mann Whitney）的分析显示，与D14峰值病毒血症的GP2相比，GRP1中的平均病毒载量明显降低：log 6.8 +/- 0.2和log 7.5 +/- 0.4（p = 0.016）;和D56病毒设定点：log5.3 +/- 0.5和log和log6.3 +/- 0.7（p = 0.03）。 在该疫苗接种组与对照组相比，记录了对SIV抗原的体液和细胞反应。最吸引人的是，与对照动物相比，在针对H9生长的SIVMAC251而不是SIVMAC239进行测试时，与对照动物相比生产中和抗体。我们正在努力分子克隆SIVMAC251-CX-1伪型病毒，以解释中和的性质。这些结果表明，重组素/SIV疫苗可以刺激恒河猕猴中针对SIVMAC抗原的体液，细胞和中和免疫反应，并提出该SVV-SIV重组的潜力，以防止抗效率化的免疫缺陷综合征。