ENHANCEMENT OF HIV IMMUNOGENICITY BY INFLUENZA VIRUS

描述：（改编自申请人摘要）本研究旨在测试 增强对HIV VLP的免疫应答的假设可以通过以下方式引起： 共施用福尔马林灭活的流感病毒。我们最近发现 福尔马林灭活的流感PR 8病毒诱导抗病毒IgM和IgG， 在不存在CD 4 + T细胞的情况下的反应。免疫的CD 4缺陷型小鼠， 还发现完全保护免受活的致病性 流感病毒。我们假设流感病毒中的特定成分可能 在诱导对其他免疫系统的免疫应答中起着重要的佐剂作用， 弱抗原性免疫原，如HIV Env，即使在不存在CD 4 + T细胞的情况下， 细胞据报道，流感病毒颗粒能迅速与其他病毒结合 如水泡性口炎、辛德毕斯或劳舍尔鼠白血病病毒 颗粒，形成混合聚集体。 流感病毒结合 特异性地结合到其他细胞表面的含神经氨酸的受体， 病毒颗粒我们将检验以下假设： HIV病毒样颗粒（VLP）和流感病毒或表型 含有流感HA组分的混合HIV/流感VLP可增强 HIV VLP单独诱导的免疫应答。因为其中一个特点 HIV感染者的CD 4 + T细胞耗竭，这种方法尤其适用于 在开发有希望的治疗性HIV疫苗以增强免疫方面具有吸引力， 艾滋病患者的反应。在这项研究中，我们将首先确定， 福尔马林灭活流感病毒增强HIV引起的免疫应答 贵宾我们将把HIV VLP与福尔马林灭活的流感PR 8病毒混合， 使用它们来确定增强的抗体应答是否在 组，给予HIV VLP和灭活流感病毒的混合物 与单独使用HIV VLP的免疫相比。我们还将比较免疫反应 由表型混合的HIV/流感病毒VLP与HIV VLPS诱导， 关于HIV中和抗体的产生和HIV中的细胞因子谱 特异性T细胞我们将特别感兴趣的是在CD 4 + T细胞检测 基因敲除小鼠，如果这种免疫也可以诱导对HIV抗体应答 以及是否也将诱导HIV特异性中和抗体应答。

DESCRIPTION: (Adapted from Applicant's Abstract) This study is designed to test the hypothesis that enhanced immune responses to HIV VLPs can be elicited by co-administration of formalin-inactivated influenza virus. We recently found that formalin-inactivated influenza PR8 virus induced antiviral IgM and IgG responses in the absence of CD4+ T cells. The immunized CD4-deficient mice were also found to be completely protected against challenge with live, pathogenic influenza virus. We hypothesize that specific components in influenza virus may play an important role as an adjuvant in inducing immune responses to other weakly antigenic immunogens such as HIV Env even in the absence of CD4+ T cells. Influenza virus particles were reported to bind rapidly to other viruses such as Vesicular stomatitis, Sindbis, or Rauscher murine leukemia virus particles, forming mixed aggregates. Influenza virus binds specifically to neuraminic acid-containing receptors at the surface of other viral particles. We will test the hypothesis that immunization with mixtures of HIV virus-like particles (VLPs) and influenza virus or with phenotypically mixed HIV/influenza VLPs containing influenza HA components may enhance the immune responses induced by HIV VLPs alone. Since one of the characteristics of HIV infected patients is CD4+ T cell depletion, this approach is especially attractive in developing a promising therapeutic HIV vaccine to enhance immune responses in AIDS patients. In this study, we will first determine if formalin-inactivated influenza virus enhances immune responses elicited by HIV VLPs. We will mix HIV VLPs with formalin-inactivated influenza PR8 virus and use them to determine whether enhanced antibody responses are induced in the groups, administered a mixture of HIV VLPs and inactivated influenza virus versus immunization with HIV VLPs alone. We will also compare immune responses induced by the phenotypically mixed HIV/influenza VLPs with HIV VLPS with respect to HIV neutralizing antibody production and cytokine profiles in HIV specific T cells. We will be especially interested in testing in CD4+ T cell knock-out mice if such immunization can also induce antibody responses to HIV and whether HIV specific neutralizing antibody responses will also be induced.