Immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic HIV protein

Immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic HIV protein
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DOI:
10.1007/s00425-013-1932-y
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发表时间:
2013-10-01
期刊:
影响因子:
4.3
通讯作者:
Rosales-Mendoza, Sergio
Rosales-Mendoza, Sergio
中科院分区:
生物学2区
文献类型:
--
作者:
Govea-Alonso, Dania O.;Rubio-Infante, Nestor;Rosales-Mendoza, Sergio

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引发广泛的体液免疫反应是开发有效的艾滋病毒疫苗的关键因素。为了开发基于多表位重组蛋白的低成本候选疫苗,本研究旨在评估和表征生菜来源的 C4(V3)6 多表位蛋白的免疫原性特性。该蛋白由 V3 环组成,对应于五种不同的 HIV 分离株,包括 MN、IIIB、RF、CC 和 RU。在这项研究中,当给 BALB/c 小鼠口服时,大肠杆菌和生菜来源的 C4(V3)6 都会引发局部和全身免疫反应。更重要的是,生菜来源的 C4(V3)6 表现出比大肠杆菌来源的 C4(V3)6 更高的免疫原性潜力。此外,当将 C4(V3)6 免疫小鼠的血清反应性与携带单一 V3 序列的嵌合蛋白引起的血清反应性进行比较时,观察到了更广泛的反应。源自生菜的 C4(V3)6 已引发对 MN、RF 和 CC 分离株中的 V3 环具有阳性反应性的抗体。此外,脾细胞增殖测定表明,C4(V3)6 免疫原可诱导显着的 T 辅助反应。总而言之,这些发现解释了观察到的 C4(V3)6 多表位蛋白引发更广泛的体液反应。此外,它们为在植物细胞中生产多表位疫苗提供了进一步的验证,因为这不仅可以作为低成本表达系统,而且可以作为口服免疫原的有效递送载体。
Elicitation of broad humoral immune responses is a critical factor in the development of effective HIV vaccines. In an effort to develop low-cost candidate vaccines based on multiepitopic recombinant proteins, this study has been undertaken to assess and characterize the immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic protein. This protein consists of V3 loops corresponding to five different HIV isolates, including MN, IIIB, RF, CC, and RU. In this study, both Escherichia coli and lettuce-derived C4(V3)6 have elicited local and systemic immune responses when orally administered to BALB/c mice. More importantly, lettuce-derived C4(V3)6 has shown a higher immunogenic potential than that of E. coli-derived C4(V3)6. Moreover, when reactivity of sera from mice immunized with C4(V3)6 are compared with those elicited by a chimeric protein carrying a single V3 sequence, broader responses have been observed. The lettuce-derived C4(V3)6 has elicited antibodies with positive reactivity against V3 loops from isolates MN, RF, and CC. In addition, splenocyte proliferation assays indicate that significant T-helper responses are induced by the C4(V3)6 immunogen. Taken together, these findings account for the observed elicitation of broader humoral responses by the C4(V3)6 multiepitopic protein. Moreover, they provide further validation for the production of multiepitopic vaccines in plant cells as this serves not only as a low-cost expression system, but also as an effective delivery vehicle for orally administered immunogens.