Mucosal Antibodies

核心B将通过处理从疫苗中收集的分泌物，积极参与所有疫苗接种研究 受者和受者血清中SIV或HIV特异性IgA和Ig G抗体的检测 标本。核心B还将就收集的最佳时间和方法提供专家建议 分泌物。盲冻样本将被运往核心B进行实验抗体分析和 用于质量控制保证测试。疫苗接种后检测粘膜抗体的合理性 猕猴和人类的研究是基于初步研究结果，这些结果表明：1)非肠道 DNA/MVA疫苗免疫可诱导强大而持久的抗病毒直肠抗体反应 GM-CSF包括作为佐剂，并且2)诱导抗病毒粘膜IgA抗体反应是 与预防免疫缺陷病毒感染有关。 在目标I中，我们将检测SIVmac251 rgp130的结合抗体和不含包膜的抗体 SIVmac251病毒裂解物显示GM-CSF佐剂免疫雌性恒河猴 SIVmac239 DNA/MVA或MVA/MVA疫苗诱导小鼠体内SIV包膜和Gag/Pol特异性IgA和Ig 直肠和阴道分泌物。SIV特异性抗体将在紧接之前和每隔一段时间定量 直肠SIVmac251挑战后确定病毒血症的减少是否与抗环境水平更好地相关 与攻击前或攻击后分泌物中存在的抗GAG/POL抗体进行比较。在AIM II的前倾斜区安全和 猕猴的免疫原性研究，我们将评估GM-CSF佐剂的Clade C DNA/MVA或 MVA/MVA疫苗诱导C型HIVczm rgp120直肠和生殖道抗体的实验研究 坦桑尼亚艾滋病毒病毒裂解物。在AIM III的I期和II期研究中，GM-CSF佐剂Clade C DNA/MVA或 同样将评估MVA/MVA疫苗诱导C类HIV特异性IgA和Ig G的能力 男性和女性志愿者生殖道和直肠分泌物中的抗体。 将在这些研究中制定和验证的参考标准和程序应 事实证明，对于评估对其他C型艾滋病毒候选疫苗的抗体反应来说，这是非常宝贵的。结果是 SIV疫苗/挑战研究还应表明是否诱导抗env或抗Gag/pols粘膜 抗体反应可作为预测HIV疫苗在人体内疗效的免疫相关指标。

Core B will actively participate in all vaccination studies by processing secretions collected from vaccine recipients and quantitating SIV- or HIV-specific mucosal IgA and IgG antibodies by ELISA in these specimens. Core B will also provide expert advice regarding optimal timing and methods for collection of secretions. Blinded frozen specimens will be shipped to Core B for both experimental antibody analyses and for quality control assurance tests. Justification for measurement of mucosal antibodies in vaccinated macaques and humans is based on results of preliminary studies which suggest that 1) parenteral immunization with DNA/MVA vaccine can induce strong and long-lived antiviral rectal antibody responses if GM-CSF is included as adjuvant, and that 2) induction of antiviral mucosal IgA antibody responses is associated with protection against immunodeficiency virus infection. In Aim I, we will measure binding antibodies to SIVmac251 rgp130 and non-envelope-containing SIVmac251 viral lysate to show that immunization of female rhesus macaques with GM-CSF-adjuvanted SIVmac239 DNA/MVA or MVA/MVA vaccine induces SIV envelope- and gag/pol-specific IgA and IgG in rectal and vaginal secretions. SIV-specific antibodies will be quantitated immediately before and at intervals after rectal SIVmac251 challenge to determine if reductions in viremia correlate better with levels of anti-env versus anti-gag/pol antibodies present in secretions before or after challenge. In Aim II preclinal safety and immunogenicity studies with macaques, we will evaluate a GM-CSF-adjuvanted Clade C DNA/MVA or MVA/MVA vaccine for its ability to induce rectal and genital tract antibodies to Clade C HIVczm rgp120 and Tanzanian HIV viral lysate. In Phase I and II studies of Aim III, GM-CSF-adjuvanted Clade C DNA/MVA or MVA/MVA vaccine will similarly be evaluated for ability to induce Clade C HIV-specific IgA and IgG antibodies in genital tract and rectal secretions of male and female human volunteers. The reference standards and procedures that will be developed and validated in these studies should prove invaluable for evaluating antibody responses to other Clade C HIV vaccine candidates. The results of the SIV vaccine/challenge studies should also indicate whether induction of anti-env or anti-gag/pol mucosal antibody responses could be used as an immune correlate for predicting HIV vaccine efficacy in humans.