DNA/MVA IMMUNOGENS, CROSS-CLADE RESPONSES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 这一方案项目通过艾滋病毒疫苗试验网络（HVTN）将艾滋病毒/艾滋病疫苗纳入早期人体试验。 该疫苗包括用表达HIV Gag、Pol和Env蛋白的重组DNA引发，然后用表达相同蛋白的重组MVA加强。 DNA和MVA都表达病毒样颗粒。低剂量组（n=10）在第0和2个月接受0.3 mg JS 7 DNA，在第4和6个月接受107 TCID 50的MVA 62。高剂量组（n=30）以相同的间隔接受3 mg的JS 7 DNA和108 TCID 50的MVA 62。安慰剂组接受生理盐水（n=8）。所有接种均为肌内接种。低剂量和高剂量的疫苗在人类中均具有良好的耐受性和免疫原性。第2次MVA免疫后，77%（20/26）的高剂量组、87%（7/8）的低剂量组和无（0/8）安慰剂组接受者具有应答性CD 4 T细胞; 42%（11/26）的高剂量组、33%（3/9）的低剂量组和无（0/8）安慰剂组接受者具有应答性CD 8 T细胞。响应针对Gag~EnvPol。与T细胞应答相反，Ab应答随疫苗剂量增加而增加。在第2次MVA接种后，高剂量组中88%的动物具有抗Env结合Ab，而低剂量组中仅22%具有抗Env结合Ab。第2次MVA增加了CD 8和Ab反应，但不增加CD 4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. This Program project has resulted in the taking of an HIV/AIDS vaccine into early phase human trials through the HIV Vaccine Trials Network (HVTN). The vaccine consists of priming with a recombinant DNA expressing HIV Gag, Pol, and Env proteins and then boosting with a recombinant MVA expressing the same proteins. Both the DNA and MVA express Virus Like Particles. A low dose group (n=10) received 0.3 mg JS7 DNA at months 0 and 2, and 107 TCID50 of MVA62 at months 4 and 6. A high dose group (n=30) received 3 mg of JS7 DNA and 108 TCID50 of MVA62 at the same intervals. Placebos received saline (n=8). All inoculations were intramuscular. Both the low and high doses of the vaccine have been well tolerated and immunogenic in humans. Following the 2nd MVA immunization, 77% (20/26) of the high dose, 87% (7/8) of the low dose and none (0/8) of the placebo recipients had responding CD4 T cells; and 42% (11/26) of the high dose, 33% (3/9) of the low dose, and none (0/8) of the placebos had responding CD8 T cells. Responses were targeted to Gag~EnvPol. In contrast to the T cell responses, Ab responses increased with vaccine dose. Following the 2nd MVA inoculation, 88% of the high dose, but only 22%, of the low dose group had anti-Env binding Ab. The 2nd MVA increased the CD8 and Ab responses but not the CD4 responses.