Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Virus Res. 2012 Aug;167(2):391-6. doi: 10.1016/j.virusres.2012.05.020. Epub 2012 May 30.
MVA-B is an attenuated poxvirus vector expressing human immunodeficiency virus type 1 Env, Gag, Pol, and Nef antigens from clade B, and is considered a promising HIV/AIDS vaccine candidate. Recently, a phase I clinical trial in human healthy volunteers has shown that MVA-B is safe and highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4(+) and CD8(+) T cell responses to HIV-1 antigens, with preference for effector memory T cells; and it also triggers the induction of specific antibodies to Env in most of the vaccines. While MVA recombinants expressing HIV-1 antigens are being used or plan to use in therapeutic clinical trials, little is known on the effect of HIV-1 highly active antiretroviral therapy in MVA life cycle. To define this role, here we have evaluated in established cell cultures and human dendritic cells to what extent different HIV-1 protease inhibitors affect virus replication and expression of HIV-1 antigens during MVA-B infection. The results obtained revealed that the most commonly used HIV-1 protease inhibitors (atazanavir, ritonavir, and lopinavir) had no effect on MVA-B virus growth kinetics, even at higher concentrations than those normally used on HAART. Furthermore, expression of gp120 and the fused Gag-Pol-Nef polyprotein in permissive and non-permissive cells infected with MVA-B were also not affected. These findings are relevant information for the therapeutic use of MVA-B as an HIV-1/AIDS vaccine.
MVA-B 是一种减毒痘病毒载体，表达来自 B 型群的人类免疫缺陷病毒 1 型Env、Gag、Pol 和 Nef 抗原，被认为是一种有前途的 HIV/AIDS 疫苗候选物。最近，一项在人类健康志愿者中的 I 期临床试验表明，MVA-B 是安全且高度免疫原性的，能够诱导针对 HIV-1 抗原的广泛、多功能和持久的 CD4(+)和 CD8(+)T 细胞反应，优先诱导效应记忆 T 细胞；并且它还能在大多数疫苗中引发针对Env 的特异性抗体的诱导。虽然表达 HIV-1 抗原的 MVA 重组体正在用于或计划用于治疗性临床试验，但人们对 HIV-1 高效抗逆转录病毒疗法对 MVA 生命周期的影响知之甚少。为了确定这一作用，我们在这里评估了在已建立的细胞培养物和人树突状细胞中，不同的 HIV-1 蛋白酶抑制剂在多大程度上影响 MVA-B 感染期间病毒复制和 HIV-1 抗原的表达。研究结果表明，最常用的 HIV-1 蛋白酶抑制剂（阿扎那韦、利托那韦和洛匹那韦）对 MVA-B 病毒生长动力学没有影响，即使在高于通常用于 HAART 的浓度下也是如此。此外，在感染 MVA-B 的允许和不允许的细胞中，gp120 和融合的 Gag-Pol-Nef 多蛋白的表达也不受影响。这些发现为 MVA-B 作为 HIV-1/AIDS 疫苗的治疗用途提供了相关信息。
