HIV-1 CD4-induced (CD4i) gp120 epitope vaccines promote B and T-cell responses that contribute to reduced viral loads in rhesus macaques.
HIV-1 CD4-induced (CD4i) gp120 epitope vaccines promote B and T-cell responses that contribute to reduced viral loads in rhesus macaques.
复制标题
HIV-1 CD4诱导的（CD4I）GP120表位疫苗促进B和T细胞反应，从而导致恒河猕猴病毒载量减少。
DOI：
10.1016/j.virol.2014.10.001
复制
发表时间：
2014-12
期刊：
影响因子：
3.7
通讯作者：
Robert-Guroff, Marjorie
中科院分区：
文献类型：
--
作者：
Thomas, Michael A.;Tuero, Iskra;Demberg, Thorsten;Vargas-Inchaustegui, Diego A.;Musich, Thomas;Xiao, Peng;Venzon, David;LaBranche, Celia;Montefiori, David C.;DiPasquale, Janet;Reed, Steven G.;DeVico, Anthony;Fouts, Timothy;Lewis, George K.;Gallo, Robert C.;Robert-Guroff, Marjorie
关键词：
为了针对HIV CD4i包膜表位，我们用复制的Ad-rhFLSC(HIV-1BaLgp120与恒河猴CD4d1和D2相连)来启动恒河猴，无论是否有Ad-SIVgag和Ad-SIVnef。用重组人外周血细胞蛋白刺激猕猴。在PBMC、支气管肺泡灌洗液和直肠组织中诱导出记忆T细胞，在直肠分泌物中诱导出具有中和和ADCC活性的抗体，以及Env特异性分泌型IgA。虽然诱导了保护性中和抗体水平，但直肠攻击后SHIVSF162P4的获得并未被阻止。攻击后即刻，血清ADCC活性、PBMC和骨髓中Env特异性记忆B细胞以及全身和粘膜记忆T细胞迅速下降，并伴有迟发性记忆反应。持续的Ad复制和TLR-4佐剂所产生的先天免疫信号可能存在冲突和重新定向的适应性免疫。不同的佐剂与复制的Ad配对，或者更长的后期间隔，允许在增强之前清除病媒，可能会培养持久的T和B细胞记忆。
To target the HIV CD4i envelope epitope, we primed rhesus macaques with replicating Ad-rhFLSC (HIV-1BaLgp120 linked to macaque CD4 D1 and D2), with or without Ad-SIVgag and Ad-SIVnef. Macaques were boosted with rhFLSC protein. Memory T-cells in PBMC, bronchoalveolar lavage and rectal tissue, antibodies with neutralizing and ADCC activity, and Env-specific secretory IgA in rectal secretions were elicited. Although protective neutralizing antibody levels were induced, SHIVSF162P4 acquisition following rectal challenge was not prevented. Rapid declines in serum ADCC activity, Env-specific memory B cells in PBMC and bone marrow, and systemic and mucosal memory T cells were observed immediately post-challenge together with delayed anamnestic responses. Innate immune signaling resulting from persisting Ad replication and the TLR-4 booster adjuvant may have been in conflict and reoriented adaptive immunity. A different adjuvant paired with replicating Ad, or a longer post-prime interval allowing vector clearance before boosting might foster persistent T- and B-cell memory.
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影响因子：
3.7
作者：
Edmonds TG;Ding H;Yuan X;Wei Q;Smith KS;Conway JA;Wieczorek L;Brown B;Polonis V;West JT;Montefiori DC;Kappes JC;Ochsenbauer C
通讯作者：
Ochsenbauer C
影响因子：
3.7
作者：
Dey, Antu K.;Burke, Brian;Barnett, Susan W.
通讯作者：
Barnett, Susan W.
DOI：
10.1073/pnas.1217609110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Guan, Yongjun;Pazgier, Marzena;Lewis, George K.
通讯作者：
Lewis, George K.
影响因子：
3.7
作者：
Buckner, C;Gines, LG;Stamatatos, L
通讯作者：
Stamatatos, L
影响因子：
5.4
作者：
Barnett, Susan W.;Burke, Brian;Srivastava, Indresh K.
通讯作者：
Srivastava, Indresh K.