VACCINE USING HIV/SIV ENV, GAG, NEF & TAT ADENOVIRUS WITH PROTEIN BOOSTING

使用 HIV/SIV ENV、GAG、NEF 进行疫苗

• 批准号: 7349364
• 负责人: Marjorie Robert-Guroff
• 金额: $ 22.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349364
• 关键词: VACCINE; USING; HIV; SIV; ENV

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. We evaluated the immunogenicity of replication-competent Ad5 host range mutant recombinants (Ad5hr). Efficacy against intravenous SHIV89.6P challenge was tested. Rhesus macaques (8 per group) were primed intranasally (wk 0) and intratracheally (wk 12) with Ad5hr encoding HIVtat (group I), HIVtat + HIV89.6Penv (group II), or HIVtat + HIV89.6Penv + SIV239gag + SIV239nef (group III). Protein subunit boosts (wks 24 and 36), given according to the Ad prime, consisted of HIV Tat (in alum, SC), and HIV89.6pgp140 and SIV239 Nef , both given in MPL-SE, IM. Control animals received Ad5hr-'E3 and adjuvant only. Macaques were challenged (wk 50) with 30 MID50 SHIV89.6P. Tat-specific IFN- ' -secreting cells measured by ELISPOT were low and sporadic over the course of immunization. The number of responders was similar in the 3 vaccination groups (7/8, 6/8, and 6/8 macaques in groups I-III, respectively). Tat-specific proliferative responses were also sporadic and less frequent, with a similar response rate among groups (3/8, 4/8, and 4/8 responders in groups I-III, respectively). Potent cellular immune responses to Env peptides were seen in group II (tat/env) and III (tat/env/gag/nef). In Group III ELISPOT responses were modest to Gag and negligible to Nef. All macaques in groups II and III exhibited proliferative responses to inactivated SHIV89.6P, and in group III, 4/8 and 7/8 responded to p27 and Nef, respectively. All macaques developed binding antibodies to their respective protein boosters. Anti-Tat titers were similar in the 3 groups, and comparable anti-Env titers were exhibited in groups II and III. All macaques in group III mounted a strong antibody response to Nef

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们评估了可复制的Ad 5宿主范围突变重组体（Ad 5 hr）的免疫原性。测试针对静脉内SHIV89.6P攻击的功效。用编码HIVtat（组I）、HIVtat + HIV89.6Penv（组II）或HIVtat + HIV89.6Penv + SIV 239 gag + SIV 239 nef（组III）的Ad 5 hr鼻内（第0周）和鼻内（第12周）致敏恒河猴（每组8只）。根据Ad prime给予的蛋白亚基加强（第24和36周）由HIV达特（明矾，SC）和HIV 89.6pgp140和SIV 239 Nef组成，均以MPL-SE，IM给予。对照动物仅接受Ad 5 hr-1 E3和佐剂。用30个MID 50 SHIV89.6P攻击猕猴（第50周）。通过ELISPOT测量的Tat特异性IFN-γ分泌细胞在免疫过程中是低的和零星的。3个接种组中应答者的数量相似（组I-III中分别为7/8、6/8和6/8只猕猴）。Tat特异性增殖反应也是散发性的，频率较低，各组之间的反应率相似（组I-III中分别为3/8、4/8和4/8反应者）。在组II（达特/env）和组III（达特/env/gag/nef）中观察到对Env肽的有效细胞免疫应答。在第III组中，ELISPOT对Gag的反应是适度的，对Nef的反应可以忽略不计。组II和组III中的所有猕猴均对灭活的SHIV89.6P表现出增殖反应，而组III中，分别有4/8和7/8的猕猴对p27和Nef有反应。所有猕猴都产生了与各自蛋白质增强剂结合的抗体。3组中的抗Tat滴度相似，组II和组III中的抗Env滴度相当。第三组的所有猕猴对Nef都产生了强烈的抗体反应