Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine
Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine
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DOI：
10.1128/jvi.00285-16
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发表时间：
2016-06-01
影响因子：
5.4
通讯作者：
Kent, Stephen J.
中科院分区：
文献类型：
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作者：
Kristensen, Anne B.;Lay, William N.;Kent, Stephen J.
本研究旨在评估季节性三价灭活流感疫苗(TIV)在HIV非感染者和HIV感染者中诱导具有Fc介导功能的非中和抗体(Abs)的能力。对30名HIV阴性和27名HIV阳性的季节性流感免疫受试者进行了功能性流感特异性抗体反应的研究。所有57名受试者都接受了2015年的TIV。免疫前和免疫后4周分别用Fc受体结合试验、NK细胞活化试验和吞噬试验检测Fc介导的抗血凝素(抗HA)抗体活性。在基线时，HIV阳性组对疫苗和非疫苗流感抗原都有可检测到的功能性抗体反应，但降低了。在HIV阳性组和HIV阴性组中，TIV均能增强Fc介导的抗体应答。在HIV阳性组中普遍观察到较大的上升，因此接种后两组之间的功能性抗体应答没有差异。2015年TIV增强了HIV阴性和HIV阳性受试者对一系列流感HA蛋白的功能性流感特异性抗体反应。HIV阳性人群中功能性抗体反应的增加支持对这一高危人群进行免疫接种的建议。感染HIV与流感感染后疾病严重程度的增加有关，建议对这一目标群体进行年度流感疫苗接种。然而，与健康人相比，艾滋病毒感染者对疫苗的反应相对较差，特别是在免疫缺陷的情况下。因此，有必要在潜在的艾滋病毒感染的背景下，增加我们对流感免疫的理解。虽然抗体可以直接中和病毒，但与细胞内Fc受体的相互作用可能通过促进抗体依赖的细胞毒性(ADCC)和/或抗体依赖的吞噬作用(ADP)而在体内抗流感免疫中发挥重要作用。目前尚不清楚季节性流感疫苗诱导具有Fc介导的抗病毒活性的抗体反应的能力。探讨ADCC和ADP对流感疫苗的反应为寻求提高对流感的免疫力提供了重要的新信息。
This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV-positive group had detectable but reduced functional Ab responses to both vaccine and nonvaccine influenza antigens. TIV enhanced Fc-mediated Ab responses in both HIV-positive and HIV-negative groups. A larger rise was generally observed in the HIV-positive group, such that there was no difference in functional Ab responses between the two groups after vaccination. The 2015 TIV enhanced functional influenza-specific Ab responses in both HIV-negative and HIV-positive subjects to a range of influenza HA proteins. The increase in functional Ab responses in the HIV-positive group supports recommendations to immunize this at-risk group.IMPORTANCEInfection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy individuals, particularly if immunodeficient. There is therefore a need to increase our understanding of immunity to influenza in the context of underlying HIV infection. While antibodies can mediate direct virus neutralization, interactions with cellular Fc receptors may be important for anti-influenza immunity in vivo by facilitating antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent phagocytosis (ADP). The ability of seasonal influenza vaccines to induce antibody responses with potent Fc-mediated antiviral activity is currently unclear. Probing the ADCC and ADP responses to influenza vaccination has provided important new information in the quest to improve immunity to influenza.