Immunogenicity of virus-like Semliki Forest virus replicon particles expressing Indian HIV-1C gag, env and polRT genes
Immunogenicity of virus-like Semliki Forest virus replicon particles expressing Indian HIV-1C gag, env and polRT genes
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DOI：
10.1016/j.imlet.2017.08.019
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发表时间：
2017-10-01
影响因子：
4.4
通讯作者：
Bandivdekar, Atmaram H.
中科院分区：
文献类型：
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作者：
Ajbani, Seema P.;Velhal, Shilpa M.;Bandivdekar, Atmaram H.
开发针对人类免疫缺陷病毒-1 C亚型（HIV-1C）的疫苗是Glade C病毒高流行地区的一项重要公共卫生优先事项。本研究证明了重组Semliki森林病毒（SFV）为基础的病毒样复制子颗粒（VRP）表达印度HIV-1C env/gag/polRT基因的免疫原性。在同源初免-加强方案中用重组VRP单独或组合免疫小鼠，引起显著的抗原特异性IFN-γ T细胞应答，如通过ELISPOT测定所检测的。此外，如通过细胞内细胞因子染色测定所估计的，分别用Gag和Env构建体免疫的小鼠也引发了分泌Gag特异性TNF-α的CD 8（+）和CD 4（+）T细胞以及分泌Env特异性IL-2的T细胞。此外，在用三种VRP构建体的组合免疫的小鼠中引发HIV Pol特异性TNF-α应答。此外，如分别通过gp 120 ELISA和p24 Gag ELISA验证的，引发HIV-1C Gag和Env特异性结合抗体。与RNA复制子相比，VRP的免疫原性更高，因此VRP可能是用于控制和管理HIV/AIDS的有希望的预防和治疗候选疫苗。
Development of a vaccine targeting human immunodeficiency virus-1 subtype C (HIV-1C) is an important public health priority in regions with a high prevalence of the Glade C virus. The present study demonstrates the immunogenicity of recombinant Semliki Forest virus (SFV)-based virus-like replicon particles (VRPs) expressing Indian HIV-1C env/gag/polRT genes. Immunization of mice with recombinant VRPs in a homologous prime-boost protocol, either individually or in combination, elicited significant antigen-specific IFN-gamma T cell responses as detected by the ELISPOT assay. Additionally, Gag-specific TNF-alpha secreting CD8(+) and CD4(+) T cells and Env-specific IL-2 secreting T cells were also elicited by mice immunized with Gag and Env constructs, respectively, as estimated by intracellular cytokine staining assay. Moreover, an HIV Pol-specific TNF-alpha response was elicited in mice immunized with a combination of the three VRP constructs. Furthermore, HIV-1C Gag and Env-specific binding antibodies were elicited as verified by gp120 ELISA and p24 Gag ELISA, respectively. The immunogenicity of VRPs was found to be higher as compared to that of RNA replicons and VRPs may therefore be promising preventive and therapeutic candidate vaccines for the control and management of HIV/AIDS.