Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial.
Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial.
复制标题
DOI：
10.1371/journal.pone.0075665
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Montefiori DC
中科院分区：
文献类型：
--
作者：
Gottardo R;Bailer RT;Korber BT;Gnanakaran S;Phillips J;Shen X;Tomaras GD;Turk E;Imholte G;Eckler L;Wenschuh H;Zerweck J;Greene K;Gao H;Berman PW;Francis D;Sinangil F;Lee C;Nitayaphan S;Rerks-Ngarm S;Kaewkungwal J;Pitisuttithum P;Tartaglia J;Robb ML;Michael NL;Kim JH;Zolla-Pazner S;Haynes BF;Mascola JR;Self S;Gilbert P;Montefiori DC
HIV-1包膜糖蛋白线性表位的中和和非中和抗体具有介导抗病毒效应功能的潜力，这可能有利于疫苗诱导的保护。在此，在三项HIV-1 gp 120疫苗有效性试验（RV 144、Vax 003、Vax 004）和HIV-1感染个体中，通过使用跨越所有主要基因亚型和病毒循环重组形式（CRF）的整个共有gp 160的重叠肽阵列，评估了血浆IgG应答。在RV 144中，观察到31.2%的HIV-1感染有效性，显性应答靶向gp 120的C1、V2、V3和C5区域。对RV 144病例对照样本的分析显示，对V2 CRF01_AE的IgG与感染风险显著负相关（OR= 0.54，p=0.0042），对其他V2亚型的应答也是如此（OR=0.60-0.63，p=0.016-0.025）。对V3 CRF01_AE的应答也与感染风险呈负相关，但仅在其他抗体水平较低的疫苗接种者中，特别是Env特异性血浆伊加（OR=0.49，p=0.007）和中和抗体（OR=0.5，p=0.008）。对C1和C5的反应与感染风险无显著相关性。在Vax 003和Vax 004中，未观察到显著保护，血清IgG应答靶向与RV 144中相同的表位，除了Vax 003中的额外C1反应性和Vax 004中罕见的V2反应性。在HIV-1感染的受试者中，显性应答针对gp 120的V3和C5区域，以及gp 41的免疫显性结构域、七肽重复序列1（HR-1）和膜近端外部区域（MPER）。这些结果强调了HIV-1包膜糖蛋白上存在几个显性线性B细胞表位。他们还产生了这样的假设，即针对gp 120的V2和V3区域中的线性表位的IgG是免疫应答的复杂相互作用的一部分，其有助于RV 144中的保护。
Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and in HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 of all major genetic subtypes and circulating recombinant forms (CRFs) of the virus. In RV144, where 31.2% efficacy against HIV-1 infection was seen, dominant responses targeted the C1, V2, V3 and C5 regions of gp120. An analysis of RV144 case-control samples showed that IgG to V2 CRF01_AE significantly inversely correlated with infection risk (OR= 0.54, p=0.0042), as did the response to other V2 subtypes (OR=0.60-0.63, p=0.016-0.025). The response to V3 CRF01_AE also inversely correlated with infection risk but only in vaccine recipients who had lower levels of other antibodies, especially Env-specific plasma IgA (OR=0.49, p=0.007) and neutralizing antibodies (OR=0.5, p=0.008). Responses to C1 and C5 showed no significant correlation with infection risk. In Vax003 and Vax004, where no significant protection was seen, serum IgG responses targeted the same epitopes as in RV144 with the exception of an additional C1 reactivity in Vax003 and infrequent V2 reactivity in Vax004. In HIV-1 infected subjects, dominant responses targeted the V3 and C5 regions of gp120, as well as the immunodominant domain, heptad repeat 1 (HR-1) and membrane proximal external region (MPER) of gp41. These results highlight the presence of several dominant linear B cell epitopes on the HIV-1 envelope glycoproteins. They also generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144.
登录
查看更多内容
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：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
通讯作者：
Lanzavecchia A
影响因子：
4.6
作者：
GOUDSMIT, J;MELOEN, RH;BRASSEUR, R
通讯作者：
BRASSEUR, R
影响因子：
6.4
作者：
GRAHAM, BS;GORSE, GJ;SMITH, GE
通讯作者：
SMITH, GE
影响因子：
1.5
作者：
Binley, JM;Ditzel, HJ;Burton, DR
通讯作者：
Burton, DR