Mucosal Antibodies

核心B将通过处理从疫苗中采集的分泌物积极参与所有疫苗接种研究 接受者和定量SIV或HIV特异性粘膜伊加和IgG抗体通过ELISA在这些 标本核心项目B还将提供关于收集 分泌物。设盲冷冻标本将运送至中心B进行实验抗体分析， 进行质量控制保证测试。接种疫苗后粘膜抗体测量的依据 猕猴和人类的研究是基于初步研究的结果，这些研究表明：1）胃肠外 DNA/MVA疫苗免疫可诱导强而持久的抗病毒直肠抗体应答， 包括GM-CSF作为佐剂，并且2）诱导抗病毒粘膜伊加抗体应答， 与免疫缺陷病毒感染有关。 在目的I中，我们将测量与SIVmac 251 rgp 130和不含包膜的 SIVmac 251病毒裂解物，以显示用GM-CSF佐剂化的 SIVmac 239 DNA/MVA或MVA/MVA疫苗诱导SIV包膜和gag/pol特异性伊加和IgG， 直肠和阴道分泌物SIV特异性抗体将在临检测前和检测间隔时进行定量 在直肠SIVmac 251攻击后，确定病毒血症的减少是否与抗-env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抗体相比。在Aim II中， 在用猕猴进行的免疫原性研究中，我们将评估GM-CSF佐剂化的分化体C DNA/MVA或 MVA/MVA疫苗诱导针对进化枝C HIVczm rgp 120的直肠和生殖道抗体的能力， 坦桑尼亚艾滋病毒裂解物。在Aim III的I期和II期研究中，使用GM-CSF佐剂化的分化体C DNA/MVA或 将类似地评价MVA/MVA疫苗诱导分化体C HIV特异性伊加和IgG的能力。 男性和女性人类志愿者的生殖道和直肠分泌物中的抗体。 在这些研究中开发和验证的参比标准品和程序应 证明对评估其他进化枝C HIV候选疫苗的抗体应答非常宝贵。的结果 SIV疫苗/攻毒研究还应表明是否诱导抗env或抗gag/pol粘膜 抗体应答可用作预测HIV疫苗在人体中效力的免疫相关物。

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.