ENHANCEMENT OF HIV IMMUNOGENICITY BY INFLUENZA VIRUS

描述：(改编自申请者摘要)本研究旨在测试 假设对HIV VLP的增强免疫反应可以通过以下方式引发 福尔马林灭活流感病毒联合注射。我们最近发现 福尔马林灭活流感PR8病毒诱导抗病毒免疫球蛋白IgM和Ig G 在没有CD4+T细胞的情况下的反应。免疫的CD4缺陷小鼠为 也被发现完全保护免受挑战的活的，致病的 流感病毒。我们假设流感病毒中的特定成分可能 在诱导对其他疾病的免疫反应中发挥重要的佐剂作用 即使在没有CD4+T细胞的情况下也是弱抗原性免疫原，如HIV Env 细胞。据报道，流感病毒颗粒能迅速与其他病毒结合。 例如水疱性口炎、辛德比斯或Rauscher鼠白血病病毒 颗粒，形成混合的聚集体。流感病毒结合在一起 特异性地与另一种细胞表面的神经氨酸受体结合 病毒颗粒。我们将检验用混合疫苗进行免疫的假设 HIV病毒样颗粒(VLP)和流感病毒或具有表型 含有流感HA成分的混合HIV/流感VLP可能会增强 仅由HIV VLP单独诱导的免疫反应。因为它的一个特点是 HIV感染者是CD4+T细胞耗尽，这种方法尤其 开发有前景的治疗性艾滋病毒疫苗以增强免疫力具有吸引力 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诱导的免疫应答 VLP。我们将艾滋病毒VLP与福尔马林灭活的流感PR8病毒混合，并 使用它们来确定是否诱导了增强的抗体反应 组，给予HIV VLP和灭活流感病毒的混合物 与单独接种艾滋病毒VLP相比。我们还将比较免疫反应 由表型混合的HIV/流感VLP与HIV VLP HIV病毒中和抗体的产生及细胞因子谱 特定的T细胞。我们将对检测CD4+T细胞特别感兴趣 基因敲除小鼠，如果这种免疫也能诱导对HIV的抗体反应 以及是否也会诱导HIV特异性中和抗体反应。

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.