Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
PLoS One. 2013 Sep 3;8(9):e74820. doi: 10.1371/journal.pone.0074820. eCollection 2013.
In recent years, heterologous prime-boost vaccines have been demonstrated to be an effective strategy for generating protective immunity, consisting of both humoral and cell-mediated immune responses against a variety of pathogens including HIV-1. Previous reports of preclinical and clinical studies have shown the enhanced immunogenicity of viral vector or DNA vaccination followed by heterologous protein boost, compared to using either prime or boost components alone. With such approaches, the selection of an adjuvant for inclusion in the protein boost component is expected to impact the immunogenicity and safety of a vaccine. In this study, we examined in a mouse model the serum cytokine and chemokine profiles for several candidate adjuvants: QS-21, Al(OH)3, monophosphoryl lipid A (MPLA) and ISCOMATRIX™ adjuvant, in the context of a previously tested pentavalent HIV-1 Env DNA prime-protein boost formulation, DP6-001. Our data revealed that the candidate adjuvants in the context of the DP6-001 formulation are characterized by unique serum cytokine and chemokine profiles. Such information will provide valuable guidance in the selection of an adjuvant for future AIDS vaccine development, with the ultimate goal of enhancing immunogenicity while minimizing reactogenicity associated with the use of an adjuvant. More significantly, results reported here will add to the knowledge on how to include an adjuvant in the context of a heterologous prime-protein boost vaccination strategy in general.
近年来,异源初免-加强疫苗已被证明是一种有效的策略,可以针对多种病原体(包括 HIV-1)产生体液和细胞介导的免疫应答。先前的临床前和临床研究报告表明,与单独使用初免或加强成分相比,病毒载体或 DNA 疫苗接种后进行异源蛋白加强可提高免疫原性。通过这种方法,选择包含在蛋白加强成分中的佐剂有望影响疫苗的免疫原性和安全性。在这项研究中,我们在小鼠模型中研究了几种候选佐剂(QS-21、Al(OH)3、单磷酰脂质 A(MPLA)和 ISCOMATRIX™佐剂)的血清细胞因子和趋化因子谱,这些佐剂是在先前测试的五价 HIV-1Env DNA 初免-蛋白加强制剂 DP6-001 的背景下。我们的数据表明,在 DP6-001 制剂背景下的候选佐剂具有独特的血清细胞因子和趋化因子谱。这些信息将为未来艾滋病疫苗开发中佐剂的选择提供有价值的指导,最终目标是提高免疫原性,同时最大限度地减少佐剂使用相关的不良反应。更重要的是,这里报告的结果将有助于了解如何在异源初免-蛋白加强接种策略的背景下包含佐剂。