Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge.
Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge.
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DOI：
10.1016/j.vaccine.2011.12.131
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发表时间：
2012-02-27
期刊：
影响因子：
5.5
通讯作者：
VanCott, Thomas C.
中科院分区：
文献类型：
--
作者：
Cox, Josephine H.;Ferrari, Maria G.;Earl, Patricia;Lane, James R.;Jagodzinski, Linda L.;Polonis, Victoria R.;Kuta, Ellen G.;Boyer, Jean D.;Ratto-Kim, Silvia;Eller, Leigh-Anne;Doan-Trang Pham;Hart, Lydia;Montefiori, David;Ferrari, Guido;Parrish, Stephanie;Weiner, David B.;Moss, Bernard;Kim, Jerome H.;Birx, Deborah;VanCott, Thomas C.
本研究评估了恒河猴中使用重组DNA（rDNA）、重组MVA（rMVA）和亚单位gp 140蛋白组合的各种初免-加强疫苗方案的免疫原性和保护效力。构建rDNA和rMVA载体以表达来自HIV-1亚型CRF01_AE的Env和来自CRF01_AE或SIVmac 239的Gag-Pol。其中一种rMVA，MVA/CMDR，最近已经在人体中进行了测试。在第0和1个月（初免）以及第3和6个月（加强）进行免疫接种。引发后，HIV env特异性血清IgG检测到接受gp 140单独或rMVA，但不是在那些接受rDNA的猴子。在单独用gp 140或用rMVA加gp 140加强后，这些组中的滴度增强。接受rDNA初免的组在用含有或不含gp 140的rMVA加强后产生env特异性IgG。HIV Env-特异性血清IgG结合抗体更频繁地被引发并且具有更高的滴度，并且中和抗体的宽度随着亚基Env加强的加入而增加。通过四聚体与Mamu-A*01猕猴中Gag p11 c的结合，以及通过IFN-γ ELISPOT试验与SIV-Gag的结合，测量T细胞应答。接种后诱导T细胞应答，在用rDNA和rMVA免疫的猕猴中观察到最高应答。用新型SHIV-E病毒（具有HIV-1亚型E-Env CAR 402的SIVmac 239 Gag-Pol）静脉内攻击猕猴。在用SHIV-E攻击后，所有组中的抗体滴度均得到加强，并在4周时达到峰值。在攻击后的所有组中观察到稳健的T细胞应答，并且在用rDNA和rMVA免疫的猕猴中观察到应答的明显加强。在用rDNA致敏并用rMVA/SHIV-AE加gp 140加强的猕猴中，在峰值病毒血症和较早设定点时，RNA拷贝/ml的对数下降大于2。用其他方案免疫的猕猴中的攻击后病毒血症与对照没有显著差异。这些结果表明，gp 140亚基和SIV Gag-Pol的包含可能是控制攻击后SHIV的关键。
The current study assessed the immunogenicity and protective efficacy of various prime-boost vaccine regimens in rhesus macaques using combinations of recombinant DNA (rDNA), recombinant MVA (rMVA), and subunit gp140 protein. The rDNA and rMVA vectors were constructed to express Env from HIV-1 subtype CRF01_AE and Gag-Pol from CRF01_AE or SIVmac 239. One of the rMVAs, MVA/CMDR, has been recently tested in humans. Immunizations were administered at months 0 and 1 (prime) and months 3 and 6 (boost). After priming, HIV env-specific serum IgG was detected in monkeys receiving gp140 alone or rMVA but not in those receiving rDNA. Titers were enhanced in these groups after boosting either with gp140 alone or with rMVA plus gp140. The groups that received the rDNA prime developed env-specific IgG after boosting with rMVA with or without gp140. HIV Env-specific serum IgG binding antibodies were elicited more frequently and of higher titer, and breadth of neutralizing antibodies was increased with the inclusion of the subunit Env boost. T cell responses were measured by tetramer binding to Gag p11c in Mamu-A*01 macaques, and by IFN-gamma ELISPOT assay to SIV-Gag. T cell responses were induced after vaccination with the highest responses seen in macaques immunized with rDNA and rMVA. Macaques were challenged intravenously with a novel SHIV-E virus (SIVmac239 Gag-Pol with an HIV-1 subtype E-Env CAR402). Post challenge with SHIV-E, antibody titers were boosted in all groups and peaked at 4 weeks. Robust T cell responses were seen in all groups post challenge and in macaques immunized with rDNA and rMVA a clear boosting of responses was seen. A greater than 2 log drop in RNA copies/ml at peak viremia and earlier set point was achieved in macaques primed with rDNA, and boosted with rMVA/SHIV-AE plus gp140. Post challenge viremia in macaques immunized with other regimens was not significantly different to that of controls. These results demonstrate that a gp140 subunit and inclusion of SIV Gag-Pol may be critical for control of SHIV post challenge.
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影响因子：
4.3
作者：
Gnanakaran S;Daniels MG;Bhattacharya T;Lapedes AS;Sethi A;Li M;Tang H;Greene K;Gao H;Haynes BF;Cohen MS;Shaw GM;Seaman MS;Kumar A;Gao F;Montefiori DC;Korber B
通讯作者：
Korber B
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：
5.4
作者：
Barnett, Susan W.;Burke, Brian;Srivastava, Indresh K.
通讯作者：
Srivastava, Indresh K.
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
影响因子：
5.5
作者：
Earl PL;Cotter C;Moss B;VanCott T;Currier J;Eller LA;McCutchan F;Birx DL;Michael NL;Marovich MA;Robb M;Cox JH
通讯作者：
Cox JH