Monoclonal antibodies to the V2 domain of MN-rgp120: fine mapping of epitopes and inhibition of α4β7 binding.
Monoclonal antibodies to the V2 domain of MN-rgp120: fine mapping of epitopes and inhibition of α4β7 binding.
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DOI：
10.1371/journal.pone.0039045
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Berman PW
中科院分区：
文献类型：
--
作者：
Nakamura GR;Fonseca DP;O'Rourke SM;Vollrath AL;Berman PW
重组gp 120（MN-rgp 120）是RV 144试验中使用的AIDSVAX B/E疫苗的主要组分。这是第一次临床试验表明疫苗接种可以预防人类感染艾滋病毒。最近的RV 144保护相关性研究发现，保护与V2结构域抗体的存在相关。已经提出V2结构域中α4β7结合位点的抗体可能通过阻断病毒体识别活化T细胞上α4β7的能力来预防HIV-1感染。在这项研究中，我们研究了单克隆抗体（MAbs）对MN-rgp 120的V2结构域的特异性，并检查了这些抗体可以抑制MN-rgp 120与α4β7整联蛋白结合的可能性。从用重组包膜蛋白免疫的小鼠中分离到针对V2结构域的9个单克隆抗体。测量这些MAb抑制HIV感染、阻断gp 120与CD 4结合以及阻断MN-rgp 120与α4β7整联蛋白结合的能力。突变分析表明，8个单克隆抗体识别两个免疫显性氨基酸簇（166-168和178-183），位于C链的两端，在四链反平行片层结构，包括V1/V2结构域。这些研究表明，V2结构域的抗原结构极其复杂，并且与从HIV感染的人分离的V2结构域的MAb相比，从MN-rgp 120免疫的小鼠分离的MAb表现出高水平的菌株特异性。我们发现用MN-rgp 120免疫很容易引发针对V2结构域的抗体，其中一些能够阻断MN-rgp 120与α4β7整联蛋白的结合。
Recombinant gp120 (MN-rgp120) was a major component of the AIDSVAX B/E vaccine used in the RV144 trial. This was the first clinical trial to show that vaccination could prevent HIV infection in humans. A recent RV144 correlates of protection study found that protection correlated with the presence of antibodies to the V2 domain. It has been proposed that antibodies to the α4β7 binding site in the V2 domain might prevent HIV-1 infection by blocking the ability of virions to recognize α4β7 on activated T-cells. In this study we investigated the specificity of monoclonal antibodies (MAbs) to the V2 domain of MN-rgp120 and examined the possibility that these antibodies could inhibit the binding of MN-rgp120 to the α4β7 integrin. Nine MAbs to the V2 domain were isolated from mice immunized with recombinant envelope proteins. The ability of these MAbs to inhibit HIV infection, block the binding of gp120 to CD4, and block the binding of MN-rgp120 to the α4β7 integrin was measured. Mutational analysis showed that eight of the MAbs recognized two immunodominant clusters of amino acids (166–168 and 178–183) located at either end of the C strand within the four-strand anti-parallel sheet structure comprising the V1/V2 domain. These studies showed that the antigenic structure of the V2 domain is exceedingly complex and that MAbs isolated from mice immunized with MN-rgp120 exhibited a high level of strain specificity compared to MAbs to the V2 domain isolated from HIV-infected humans. We found that immunization with MN-rgp120 readily elicits antibodies to the V2 domain and some of these were able to block the binding of MN-rgp120 to the α4β7 integrin.
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影响因子：
5.4
作者：
FUNG, MSC;SUN, CRY;HO, DD
通讯作者：
HO, DD
影响因子：
5.4
作者：
Gorny, MK;Stamatatos, L;Zolla-Pazner, S
通讯作者：
Zolla-Pazner, S
影响因子：
5.4
作者：
GORNY, MK;MOORE, JP;ZOLLAPAZNER, S
通讯作者：
ZOLLAPAZNER, S
影响因子：
6.4
作者：
Berman, PW;Murthy, KK;Obijeski, JF
通讯作者：
Obijeski, JF
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH