Influence of HIV and HCV on T cell antigen presentation and challenges in the development of vaccines
Influence of HIV and HCV on T cell antigen presentation and challenges in the development of vaccines
复制标题
HIV和HCV对T细胞抗原呈递的影响以及疫苗开发中的挑战
DOI：
--
复制
发表时间：
2014
影响因子：
5.2
通讯作者：
S. Gaudieri
中科院分区：
文献类型：
--
作者：
M. John;S. Gaudieri
开发针对HIV和丙型肝炎病毒（HCV）的有效疫苗的一些核心挑战是相似的。这两种感染都是由小的、高度可变的、快速复制的RNA病毒引起的，RNA病毒具有在人类宿主中建立长期慢性病原性感染的能力。HIV在全球已造成6000万人感染，HCV感染1.8亿人，这两种病毒可能通过常见的血液传播、性传播或垂直传播在某些人群中共存。这两种病原体的持久性是通过逃避内在的、先天的和适应性的免疫防御来实现的，但具有一些不同的机制，反映了它们在进化史、复制特征、细胞嗜性以及粘膜与全身和肝脏免疫应答的可见性方面的差异。一个有效的和持久的抗体和T细胞反应是未来的艾滋病毒和HCV疫苗的可能要求。也许这两种疫苗设计挑战之间最大的区别是，在HCV中，可以在自发解决急性感染的人中发现保护性免疫的天然模型。这样的自发消退者表现出持久的和功能性的CD 4+和CD 8 + T细胞应答（Diepolder等人，1995;库珀等人，1999; Thimme等人，2001; Grakoui等人，2003;劳尔等人，2004; Schulze Zur Wiesch等人，2012年）。然而，频繁的再感染表明部分或缺乏对异源HCV毒株的保护性免疫，可能表明循环HCV基因型和亚型的遗传多样性程度。在HIV中没有保护性免疫的天然模型，然而，对“精英控制者”或在没有抗逆转录病毒治疗的情况下持久抑制血浆HIV RNA水平的个体的研究提供了CD 8 + T细胞应答在控制病毒血症和限制已建立感染中的储库负担方面的最强有力证据。在这里，我们比较和对比HIV和HCV使用的免疫逃避的具体机制，这颠覆了适应性人类白细胞抗原（HLA）限制性T细胞免疫的自然感染，以及这些设计有效的预防性或治疗性疫苗所面临的挑战。
Some of the central challenges for developing effective vaccines against HIV and hepatitis C virus (HCV) are similar. Both infections are caused by small, highly mutable, rapidly replicating RNA viruses with the ability to establish long-term chronic pathogenic infection in human hosts. HIV has caused 60 million infections globally and HCV 180 million and both viruses may co-exist among certain populations by virtue of common blood-borne, sexual, or vertical transmission. Persistence of both pathogens is achieved by evasion of intrinsic, innate, and adaptive immune defenses but with some distinct mechanisms reflecting their differences in evolutionary history, replication characteristics, cell tropism, and visibility to mucosal versus systemic and hepatic immune responses. A potent and durable antibody and T cell response is a likely requirement of future HIV and HCV vaccines. Perhaps the single biggest difference between the two vaccine design challenges is that in HCV, a natural model of protective immunity can be found in those who resolve acute infection spontaneously. Such spontaneous resolvers exhibit durable and functional CD4+ and CD8+ T cell responses (Diepolder et al., 1995; Cooper et al., 1999; Thimme et al., 2001; Grakoui et al., 2003; Lauer et al., 2004; Schulze Zur Wiesch et al., 2012). However, frequent re-infection suggests partial or lack of protective immunity against heterologous HCV strains, possibly indicative of the degree of genetic diversity of circulating HCV genotypes and subtypes. There is no natural model of protective immunity in HIV, however, studies of “elite controllers,” or individuals who have durably suppressed levels of plasma HIV RNA without antiretroviral therapy, has provided the strongest evidence for CD8+ T cell responses in controlling viremia and limiting reservoir burden in established infection. Here we compare and contrast the specific mechanisms of immune evasion used by HIV and HCV, which subvert adaptive human leukocyte antigen (HLA)-restricted T cell immunity in natural infection, and the challenges these pose for designing effective preventative or therapeutic vaccines.
登录
查看更多内容
影响因子：
56.9
作者：
Carrington, M;Nelson, GW;O'Brien, SJ
通讯作者：
O'Brien, SJ
影响因子：
29.4
作者：
Lauer, GM;Barnes, E;Klenerman, P
通讯作者：
Klenerman, P
影响因子：
32.4
作者：
Cohen, GB;Gandhi, RT;Baltimore, D
通讯作者：
Baltimore, D
影响因子：
32.4
作者：
Cooper, S;Erickson, AL;Walker, CM
通讯作者：
Walker, CM