Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.
Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.
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接种疫苗的非人类灵长类动物中HIV-1中和抗体的结构和遗传趋同。
DOI：
10.1371/journal.ppat.1009624
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发表时间：
2021-06
期刊：
影响因子：
6.7
通讯作者：
Saunders KO
中科院分区：
文献类型：
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作者：
Cai F;Chen WH;Wu W;Jones JA;Choe M;Gohain N;Shen X;LaBranche C;Eaton A;Sutherland L;Lee EM;Hernandez GE;Wu NR;Scearce R;Seaman MS;Moody MA;Santra S;Wiehe K;Tomaras GD;Wagh K;Korber B;Bonsignori M;Montefiori DC;Haynes BF;de Val N;Joyce MG;Saunders KO
HIV-1疫苗开发的主要目标是持续诱导保护性中和抗体。虽然已经从多个HIV感染个体中分离出高度相似的中和抗体（nAb），但尚不清楚疫苗接种是否能在遗传多样性的灵长类动物中始终引发高度相似的nAb。在这里，我们显示在三个远交猕猴，免疫与Env elastina基因型和表型保守的nAb反应。从这些接种疫苗的猕猴中，我们分离出四种抗体谱系，它们在免疫球蛋白可变性、多样性和连接基因片段使用方面具有共性。两种最相似抗体的抗原结合片段的原子水平结构显示出几乎相同的互补位。四种疫苗诱导的nAb中的每一种的Env结合模式与先前已知的单克隆HIV-1中和抗体不同，但彼此几乎相同。这些抗体的相似性表明，远交灵长类动物中的免疫系统可以以类似的结构和基因型解决方案对HIV-1 Env疫苗接种做出反应，以识别特定的中和表位。这些结果支持HIV-1的合理疫苗设计，其目的是在遗传多样性灵长类动物中可重复地引发具有能够结合保守表位的特异性互补位结构的nAb。灵长类动物的免疫系统会产生一系列不同的病原体结合蛋白，称为抗体。灵长类动物的抗体库必须是多样的，以响应许多不同病原体的感染。在这项研究中，我们的特点是HIV-1抑制性抗体的结构和遗传特征，从接种疫苗的猴子作为人类疫苗接种的模型。我们发现，单个猴子通过产生高度相似的HIV-1中和抗体对HIV疫苗作出反应。这些抗体具有几乎相同的结构和基因组成。因此，不同猴子的免疫系统产生了抑制病毒蛋白功能和传染性的共同解决方案。疫苗在多个接受者中的成功可能通过免疫系统可重复地设计共同抗体解决方案以攻击病原体上的脆弱位点的能力来增强。
A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes. The primate immune system generates a diverse repertoire of pathogen-binding proteins called antibodies. Primate antibody repertoires must be diverse to respond to infection by many different pathogens. In this study, we characterized the structure and genetic features of HIV-1 inhibitory antibodies from vaccinated monkeys as a model for human vaccination. We found that individual monkeys responded to HIV vaccination by generating highly similar HIV-1 neutralizing antibodies. The antibodies had nearly identical structures and genetic makeups. Thus, the immune systems of different monkeys generate a common solution for inhibiting viral protein function and infectivity. Success of vaccines in multiple recipients may be augmented by the ability of immune systems to reproducibly devise a common antibody solution to attack vulnerable sites on pathogens.
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影响因子：
16.6
作者：
Cao L;Pauthner M;Andrabi R;Rantalainen K;Berndsen Z;Diedrich JK;Menis S;Sok D;Bastidas R;Park SR;Delahunty CM;He L;Guenaga J;Wyatt RT;Schief WR;Ward AB;Yates JR 3rd;Burton DR;Paulson JC
通讯作者：
Paulson JC
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.4
作者：
Go, Eden P.;Irungu, Janet;Desaire, Heather
通讯作者：
Desaire, Heather
影响因子：
64.5
作者：
Bonsignori M;Zhou T;Sheng Z;Chen L;Gao F;Joyce MG;Ozorowski G;Chuang GY;Schramm CA;Wiehe K;Alam SM;Bradley T;Gladden MA;Hwang KK;Iyengar S;Kumar A;Lu X;Luo K;Mangiapani MC;Parks RJ;Song H;Acharya P;Bailer RT;Cao A;Druz A;Georgiev IS;Kwon YD;Louder MK;Zhang B;Zheng A;Hill BJ;Kong R;Soto C;NISC Comparative Sequencing Program;Mullikin JC;Douek DC;Montefiori DC;Moody MA;Shaw GM;Hahn BH;Kelsoe G;Hraber PT;Korber BT;Boyd SD;Fire AZ;Kepler TB;Shapiro L;Ward AB;Mascola JR;Liao HX;Kwong PD;Haynes BF
通讯作者：
Haynes BF
个体化 V 基因数据库的产生揭示了高水平的免疫球蛋白遗传多样性。
影响因子：
16.6
作者：
通讯作者：
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