Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin HIV AIDS. 2014 May;9(3):257-62. doi: 10.1097/COH.0000000000000051.
In this review, the roles of Fc-gamma receptor polymorphisms are discussed in regards to HIV-1 vaccine efficacy, HIV acquisition, and disease progression. In addition, the significance of the neonatal immunoglobulin G (IgG) Fc receptor and potential effects of the aggregated immunoglobulin A Fc receptor (FcalphaR) are addressed.
Fc receptors undoubtedly play an important role in antibody-mediated action in HIV infection and vaccines. Several studies have determined an association between polymorphic variants of Fc-gamma-RIIA and Fc-gamma-RIIIA in the acquisition and progression of HIV-1 infection, and in responses to vaccination regimens. A rather complex relationship exists between the relative affinity of these molecules and their impact on HIV disease acquisition and progression and HIV vaccine efficacy.
The discrepancies between different investigations of the role of Fc receptor polymorphisms appear to derive from the complex nature of the Fc receptor functions, including factors such as epistatic interactions and the race, sex, age, and relative risk behavior of the investigated individuals. Furthermore, Fc receptors in nonhuman primates (NHPs), the key model to study an AIDS-like disease in an animal model, appear to be even more diverse than in humans, and the function of these proteins has not been extensively explored. Given the critical role of Fc receptors in antibody-mediated function in humans and NHP, more investigations are needed to fully understand and exploit these functions for vaccine design.
在这篇综述中,讨论了 Fc-γ 受体多态性在 HIV-1 疫苗疗效、HIV 感染和疾病进展中的作用。此外,还讨论了新生儿免疫球蛋白 G(IgG)Fc 受体的意义以及聚集免疫球蛋白 A Fc 受体(FcalphaR)的潜在影响。
Fc 受体无疑在 HIV 感染和疫苗中的抗体介导作用中发挥重要作用。几项研究已经确定了 Fc-γ-RIIA 和 Fc-γ-RIIIA 的多态变体与 HIV-1 感染的获得和进展以及对疫苗接种方案的反应之间存在关联。这些分子的相对亲和力与其对 HIV 疾病获得和进展以及 HIV 疫苗疗效的影响之间存在相当复杂的关系。
Fc 受体多态性作用的不同研究之间的差异似乎源于 Fc 受体功能的复杂性质,包括上位相互作用以及所研究个体的种族、性别、年龄和相对风险行为等因素。此外,非人类灵长类动物(NHP)中的 Fc 受体(研究 AIDS 样疾病的关键模型)似乎比人类更加多样化,这些蛋白质的功能尚未得到广泛探索。鉴于 Fc 受体在人类和 NHP 中抗体介导功能中的关键作用,需要进行更多的研究来充分理解和利用这些功能来设计疫苗。