IMPORTANCE OF ANTIBODY ISOTYPE IN VAGINAL HIV TRANSMISSION

抗体同种型在艾滋病毒阴道传播中的重要性

• 批准号: 8358084
• 负责人: Ronald S. Veazey
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358084
• 关键词: Administrative Supplement; Antibodies; Funding; Grant; HIV; HIV Infections; Immunoglobulin A; Immunoglobulin G; Intestines; J-Chain Immunoglobulins; Membrane; Molecular Conformation; Mucous Membrane; National Center for Research Resources; Paper; Pathogenesis; Preparation; Primates; Principal Investigator; Rectum; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; Vagina; cost; intravenous administration; neutralizing antibody; prevent; research study; simian human immunodeficiency virus; transmission process; vaginal transmission

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. It is now clear that intestine and other mucosal tissues are of major importance in both the transmission as well as the early pathogenesis of HIV infection. We are currently determining whether antibodies of different isotypes are better for protecting the vaginal vault, and performed experiments to determine if there was preferential secretion. Last year we showed that HIV-specific IgA and IgG are preferentially secreted from the intestine (rectum) and vagina, respectively following intravenous administration of HIV-specific antibodies. Originally this was performed using antibodies against the membrane proximal external region (MPER) of HIV (2F5) but after receiving an administrative supplement to Dennis Burton at Scripps this year, we have also pursued this with other non-neutralizing antibodies (b12). However, we have not been able to demonstrate different levels of protection from vaginal transmission when any antibody to date in the IgA isotypes were used, and in fact IgG levels do seem to correlate better with protection. Whether this is a factor of not having the appropriate conformation (J-chain etc) of the IgA version of the same antibody is now being investigated. Further, we have other ongoing studies to determine whether the same effect occurs with different levels of neutralizing antibodies (2F5 vs b12). In CHAVI we have largely switched to examining MPER antibodies (2F5) as these are more conserved and apparently equally as effective in preventing transmission, especially when in IgG forms, and a paper is currently in preparation describing the distribution and efficacy of these antibodies in preventing vaginal SHIV transmission.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 现在很明显，肠道和其他粘膜组织在传播以及HIV感染的早期发病机理中都至关重要。 我们目前正在确定不同同种型的抗体是否更适合保护阴道库，并进行了实验以确定是否存在优先分泌。 去年，我们表明HIV特异性的IgA和IgG优先从肠道（直肠）和阴道分泌，分别在静脉内给予HIV特异性抗体后。 最初是使用针对HIV的膜近端外部区域（MPER）的抗体（2F5）进行的，但是在今年在Scripps接受了Dennis Burton的行政补充后，我们还与其他非中和抗体进行了此过程（B12）。但是，当使用IGA同种型中的任何抗体时，我们无法证明与阴道传播的不同水平，并且实际上IgG水平似乎与保护更好地相关。 现在正在研究同一抗体的IgA版本的适当构象（J链等），现在正在研究这是一个因素。此外，我们还进行了其他正在进行的研究，以确定是否具有不同水平的中和抗体（2f5 vs b12）的效果。 在Chavi中，我们已大部分转向检查MPER抗体（2F5），因为它们更保守，并且显然同样有效地防止传播，尤其是在IgG形式时，并且目前正在准备一份论文，以准备描述这些抗体在防止阴道SHIV传播方面的分布和功效。