Wang Shixia, Yates Nicole L, Pollara Justin, Voronin Yegor, Stanfield-Oakley Sherry, Han Dong, Hu Guangnan, Li Wei, Ferrari Guido, Tomaras Georgia D, Lu Shan
University of Massachusetts Medical School, Worcester, MA, USA.
Worcester HIV Vaccine Inc., Worcester, MA, USA.
NPJ Vaccines. 2022 Feb 9;7(1):18. doi: 10.1038/s41541-022-00441-9.
Since publishing our original reports on the safety and immunogenicity of a polyvalent DNA prime-protein boost HIV vaccine (PDPHV) which elicited high titer antibody responses with broad specificity, neutralizing activities to multiple HIV-1 subtypes, as well as poly-functional T cell responses, accumulated findings from other HIV vaccine studies indicated the important roles of Ig isotype distribution, Fc medicated functions and the persistence of memory immune responses which were not studied in previous PDPHV related reports. The current report provides further detailed characterization of these parameters in human volunteers receiving the PDPHV regimen. Antibody responses were assessed using IgG isotype and gp70-V1V2-binding ELISAs, peptide arrays, and antibody-dependent cellular cytotoxicity (ADCC) assays. B cell ELISPOT was used to detect gp120-specific memory B cells. Our results showed that the gp120-specific antibodies were primarily of the IgG1 isotype. HIV-1 envelope protein variable regions V1 and V2 were actively targeted by the antibodies as determined by specific binding to both peptide and V1V2-carrying scaffolds. The antibodies showed potent and broad ADCC responses. Finally, the B cell ELISPOT analysis demonstrated persistence of gp120-specific memory B cells for at least 6 months after the last dose. These data indicate that broadly reactive binding Abs and ADCC responses as well as durable gp120-specific memory B cells were elicited by the polyvalent heterologous prime-boost vaccination regimens and showed great promise as a candidate HIV vaccine.
自从我们发表了关于一种多价DNA初免-蛋白加强型HIV疫苗（PDPHV）的安全性和免疫原性的原始报告以来，该疫苗引发了具有广泛特异性的高滴度抗体反应、对多种HIV-1亚型的中和活性以及多功能T细胞反应。其他HIV疫苗研究积累的结果表明，Ig同种型分布、Fc介导的功能以及记忆免疫反应的持久性具有重要作用，而这些在之前与PDPHV相关的报告中并未进行研究。本报告进一步详细描述了接受PDPHV方案的人类志愿者中这些参数的特征。使用IgG同种型和gp70-V1V2结合ELISA、肽阵列以及抗体依赖性细胞毒性（ADCC）试验评估抗体反应。B细胞ELISPOT用于检测gp120特异性记忆B细胞。我们的结果表明，gp120特异性抗体主要为IgG1同种型。通过与肽和携带V1V2的支架特异性结合确定，HIV-1包膜蛋白可变区V1和V2是抗体的活跃靶向区域。这些抗体表现出强大而广泛的ADCC反应。最后，B细胞ELISPOT分析表明，最后一剂疫苗接种后至少6个月，gp120特异性记忆B细胞持续存在。这些数据表明，多价异源初免-加强疫苗接种方案引发了广泛反应性结合抗体和ADCC反应以及持久的gp120特异性记忆B细胞，作为一种候选HIV疫苗显示出巨大的前景。
