Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
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DOI：
10.1371/journal.pone.0045267
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cunha-Neto E
中科院分区：
文献类型：
--
作者：
Almeida RR;Rosa DS;Ribeiro SP;Santana VC;Kallás EG;Sidney J;Sette A;Kalil J;Cunha-Neto E
以T细胞为基础的疫苗方法已经出现，以对抗艾滋病毒-1/艾滋病。广泛的、多功能的和细胞毒性的CD4+T细胞反应与控制HIV-1复制有关，这支持将CD4+T细胞表位包括在疫苗中。一种成功的HIV-1疫苗还应该设计成克服病毒遗传多样性，并能够在来自不同的携带人类白细胞抗原的人群中的高比例免疫个人中产生免疫力。在这项研究中，我们合理地设计了一种多表位DNA疫苗，以诱导针对HIV-1 M组共识序列中高度保守和混杂的多肽的广泛和跨分支的CD4+T细胞反应。利用TEPITOPE算法，我们在HIV-1 M群的Gag、Pol、Nef、Vif、Vpr、Rev和VPu的共同序列中鉴定了27个保守的、多个与HLA-DR结合的多肽。这些多肽在体外平均与17个测试的HLA-DR分子中的12个结合，还与几个分子结合，如HLA-DP、-DQ和小鼠IAB和IAD。来自感染不同HIV-1变异体的患者的PBMC识别出27个多肽中的16个，其中72%的患者至少识别一个多肽。用编码这些多肽的核酸疫苗(HIVBr27DNA疫苗)免疫BALB/c小鼠，可诱导其中11个多肽产生干扰素-γ，8个和6个多肽分别能刺激CD_4+和CD_8~+T细胞增殖。HIVBr27免疫可诱导针对几种HIV-1多肽变异体的交叉T细胞反应。CD_4~+和CD_8~+T细胞可同时增殖并产生干扰素-γ和肿瘤坏死因子-α。这一疫苗概念可以应对艾滋病毒-1基因多样性，并提供更大的人口覆盖率，这是有效抗击艾滋病毒-1/艾滋病战略的理想特征。
T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4+ T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4+ T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be designed to overcome viral genetic diversity and be able to confer immunity in a high proportion of immunized individuals from a diverse HLA-bearing population. In this study, we rationally designed a multiepitopic DNA vaccine in order to elicit broad and cross-clade CD4+ T-cell responses against highly conserved and promiscuous peptides from the HIV-1 M-group consensus sequence. We identified 27 conserved, multiple HLA-DR-binding peptides in the HIV-1 M-group consensus sequences of Gag, Pol, Nef, Vif, Vpr, Rev and Vpu using the TEPITOPE algorithm. The peptides bound in vitro to an average of 12 out of the 17 tested HLA-DR molecules and also to several molecules such as HLA-DP, -DQ and murine IAb and IAd. Sixteen out of the 27 peptides were recognized by PBMC from patients infected with different HIV-1 variants and 72% of such patients recognized at least 1 peptide. Immunization with a DNA vaccine (HIVBr27) encoding the identified peptides elicited IFN-γ secretion against 11 out of the 27 peptides in BALB/c mice; CD4+ and CD8+ T-cell proliferation was observed against 8 and 6 peptides, respectively. HIVBr27 immunization elicited cross-clade T-cell responses against several HIV-1 peptide variants. Polyfunctional CD4+ and CD8+ T cells, able to simultaneously proliferate and produce IFN-γ and TNF-α, were also observed. This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS.
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影响因子：
3.8
作者：
Bansal, A;Gough, E;Goepfert, PA
通讯作者：
Goepfert, PA
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
5.4
作者：
BenMohamed, L;Bertrand, G;Nesburn, AB
通讯作者：
Nesburn, AB
影响因子：
5.4
作者：
Depla, Erik;Van der Aa, Annegret;Meheus, Lydie
通讯作者：
Meheus, Lydie
影响因子：
4.4
作者：
Bijker, Martijn S.;van den Eeden, Susan J. F.;van der Burg, Sjoerd H.
通讯作者：
van der Burg, Sjoerd H.