ANTIBODY EFFECTOR FUNCTION PROTECTION AGAINST HIV-1

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 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 研究中心，而研究中心不一定是研究者所在的机构。 中和抗体对HIV疫苗很重要。 被动抗体转移已经表明，中和抗体在高浓度下保护免受带有HIV-1包膜的致病性SHIV的阴道攻击。 中和抗体的保护机制，特别是Fc介导的效应子功能的作用尚未确定。 分泌型伊加的作用以及粘膜和全身中和抗体之间的相互作用可能很重要，但尚未研究。 2007年和2998年，进行了一次低剂量重复接触实验。 总共17只动物每周用静脉内抗体处理，每周两次阴道内用SHIV 162 p3攻击，直到确认感染和/或bDNA。 所有动物在第一次激发前35天用Depo-provera处理，此后每21天用Depo-provera处理，以维持变薄的阴道上皮。 对照动物（n=7）用相当于lml/kg的剂量的对照（PBS）抗体处理。 LL突变体组（n=5）和b12野生型组（n=5）中的动物用其各自的抗体以1 ml/kg的剂量处理。 攻毒剂量范围为3 TCID 50 - 29 TCID 50。 所有对照组动物在8 - 10天的一系列攻击后均被感染。16（平均值= 11.7+/- 3.1 SD）。 所有LL突变动物在17个月的一系列攻击后都被感染。36（平均值= 26.8 +/- 9.5 SD）。 5只b12动物中有4只在8-50次攻毒后感染（平均值= 27.8 +/- 18.9 SD）。 最后一只b12动物在56次攻击后抵抗了感染（其中6只没有抗体处理）。

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. Neutralizing antibodies are important for HIV vaccines. Passive antibody transfer has shown that neutralizing antibodies, at high concentrations, protect from vaginal challenge with pathogenic SHIVs bearing the HIV-1 envelope. The mechanisms of protection by neutralizing antibody and in particular, the role of Fc-mediated effector function have not been defined. The role of secretory IgA and the interplay between mucosal and systemic neutralizing antibodies is probably important but has not been studied. In 2007 and 2998, a low-dose, repeated exposure experiment was conducted. A total of 17 animals were treated weekly with intravenous antibody and challenged twice weekly intravaginally with SHIV 162p3 until infection was confirmed and/or bDNA. All animals were treated with Depo-provera 35 days prior to the first challenge and every 21 days thereafter to maintain a thinned vaginal epithelium. Control animals (n=7) were treated with control (PBS) antibody at a dose equivalent to 1 ml/kg. Animals in the LL mutant group (n=5) and the b12 wild type group (n=5) were treated with their respective antibodies at a dose of 1 ml/kg. Challenge doses ranged from 3 TCID50 to 29 TCID50. All control animals became infected after a range of challenges from 816 (average = 11.7+/- 3.1 SD). All LL mutant animals became infected after a range of challenged from 1736 (average = 26.8 +/- 9.5 SD). 4 of 5 b12 animals became infected after a range of challenges from 8-50 (average = 27.8 +/- 18.9 SD). The final b12 animal resisted infection after 56 challenges (6 of those without antibody treatment).