Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001
Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001
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DOI：
10.1128/jvi.01458-16
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发表时间：
2016-11-01
影响因子：
5.4
通讯作者：
Wang, Shixia
中科院分区：
文献类型：
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作者：
Costa, Matthew R.;Pollara, Justin;Wang, Shixia
HIV-1只有在感染数年后才能在非常小的个体亚群中引发广泛有效的中和抗体，因此，很难设计出引发这些类型抗体的疫苗。RV 144试验表明，中度保护是可能的，这种保护可能与抗体依赖性细胞毒性（ADCC）活性相关。我们之前的研究表明，在HIV疫苗I期试验（DP 6 -001试验）中，多价Env DNA引物-蛋白加强制剂可以引发具有阳性中和活性的强效和广泛反应性的gp 120特异性抗体。在这里，我们报告了从DP 6 -001试验中的疫苗接种者中分离的HIV-1 Env特异性人单克隆抗体（hMAb）的生产和分析。对于该初步报告，来自DP 6 -001试验中的4名疫苗接种者的13种hMAb显示与疫苗免疫原自体和异源的不同亚型的gp 120蛋白广泛结合。免疫血清和分离的单克隆抗体均存在同样的交叉反应性Fc受体介导的功能活性，包括ADCC和抗体依赖性细胞吞噬作用（ADCP）活性，证实了DNA引发蛋白加强疫苗接种诱导的非中和功能性hMAb。广泛反应的hMAb的健康人类志愿者接种疫苗的启发证实了价值的多价制剂在这种HIV疫苗design.IMPORTANCEThe Fc受体介导的保护性抗体反应的作用越来越受到关注，由于其潜在的贡献，对HIV-1感染的低水平保护，他们提供了在RV 144试验。与此同时，来自其他人类HIV疫苗研究的关于hMab的信息非常有限。在本研究中，当使用多价DNA引物-蛋白加强疫苗制剂时，来自接种疫苗的人的免疫血清和单克隆抗体不仅显示出高水平的ADCC和ADCP活性，而且还显示出交叉亚型ADCC和ADCP活性。
HIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that moderate protection is possible and that this protection may correlate with antibody-dependent cellular cytotoxicity (ADCC) activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, the DP6-001 trial, a polyvalent Env DNA prime-protein boost formulation could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc receptor-mediated functional activities, including ADCC and antibody-dependent cellular phagocytosis (ADCP) activities, were present with both immune sera and isolated MAbs, confirming the induction of nonneutralizing functional hMAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive hMAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design.IMPORTANCEThe roles of Fc receptor-mediated protective antibody responses are gaining more attention due to their potential contribution to the low-level protection against HIV-1 infection that they provided in the RV144 trial. At the same time, information about hMabs from other human HIV vaccine studies is very limited. In the current study, both immune sera and monoclonal antibodies from vaccinated humans showed not only high-level ADCC and ADCP activities but also cross-subtype ADCC and ADCP activities when a polyvalent DNA prime-protein boost vaccine formulation was used.