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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们评估了具有复制能力的Ad5宿主范围突变重组体(Ad5hr)的免疫原性。对静脉注射SHIV89.6P攻击的效果进行了测试。恒河猴(每组8只)鼻内(Wk 0)和气管内(Wk 12)分别用编码HIVtat的Ad5hr(组I)、HIVtat+HIV89.6Penv(组II)或HIVtat+HIV89.6Penv+SIV239gag+SIV239 nef(组III)。根据Ad Prime给出的蛋白质亚基Boost(WK24和36)由HIV Tat(在明矾中，SC)和HIV89.6pgp140和SIV239Nef组成，两者都在MPL-SE，IM中给出。对照组只接种Ad5hr-‘E3和佐剂，猕猴用30MID50 SHIV89.6P攻击(Wk50)，ELISPOT检测TAT特异性干扰素-’分泌细胞在免疫过程中呈低而散在分布。3个接种组的应答人数相似(I-III组分别为7/8、6/8和6/8)。TAT特异性的增殖反应也是零星的，而且不太常见，各组之间的应答率相似(I-III组分别有3/8、4/8和4/8的应答者)。第二组(TAT/env)和第三组(Tat/env/Gag/nef)有较强的细胞免疫应答。在第三组中，Elispot的回答是温和的，对Nef的回答可以忽略不计。组II和组III对灭活的SHIV89.6P均有增殖反应，组III分别有4/8和7/8对p27和Nef有反应。所有的猕猴都产生了对它们各自的蛋白质增强剂的结合抗体。3组的抗TAT效价相似，II组和III组的抗Env效价相近。III组的猕猴对Nef均有较强的抗体反应

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