Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization.
Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization.
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DOI：
10.1038/ncomms7565
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发表时间：
2015-04-10
影响因子：
16.6
通讯作者：
Seder, Robert A.
中科院分区：
文献类型：
--
作者：
Francica, Joseph R.;Sheng, Zizhang;Zhang, Zhenhai;Nishimura, Yoshiaki;Shingai, Masashi;Ramesh, Akshaya;Keele, Brandon F.;Schmidt, Stephen D.;Flynn, Barbara J.;Darko, Sam;Lynch, Rebecca M.;Yamamoto, Takuya;Matus-Nicodemos, Rodrigo;Wolinsky, David;Nason, Martha;Valiante, Nicholas M.;Malyala, Padma;De Gregorio, Ennio;Barnett, Susan W.;Singh, Manmohan;O'Hagan, Derek T.;Koup, Richard A.;Mascola, John R.;Martin, Malcolm A.;Kepler, Thomas B.;Douek, Daniel C.;Shapiro, Lawrence;Seder, Robert A.
开发预测性动物模型来评估候选疫苗和感染如何影响包膜（Env）特异性抗体的个体发育对于HIV疫苗的开发至关重要。在这里，我们使用两个非人灵长类动物模型来比较抗原持久性，多样性和先天免疫的作用。我们对HIV Env特异性B细胞受体对SHIVAD8感染和Env蛋白接种8种不同佐剂的反应进行了纵向分析。具有更高病毒载量和更大Env多样性的SHIVAD 8感染动物的子集显示出与随时间增加的体细胞超突变（SHM）水平相关的中和增加。佐剂的使用导致ELISA滴度增加，但不影响平均SHM水平或CDR H3长度。我们的研究显示了Env特异性B细胞的个体发育如何被追踪，并提供了对开发中和抗体的要求的见解，这些中和抗体应有助于转化为人类疫苗研究。 艾滋病毒疫苗的开发将通过具有预测性的动物模型来促进。在这里，作者使用两种非人灵长类动物模型来比较自然感染和不同佐剂对抗原持久性、多样性和体液免疫的影响。
Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIVAD8 infection and Env protein vaccination with eight different adjuvants. A subset of the SHIVAD8-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies. HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.
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影响因子：
64.8
作者：
Huang J;Ofek G;Laub L;Louder MK;Doria-Rose NA;Longo NS;Imamichi H;Bailer RT;Chakrabarti B;Sharma SK;Alam SM;Wang T;Yang Y;Zhang B;Migueles SA;Wyatt R;Haynes BF;Kwong PD;Mascola JR;Connors M
通讯作者：
Connors M
影响因子：
1.8
作者：
Ketloy, Chutitorn;Engering, Anneke;Ruxrungtham, Kiat
通讯作者：
Ruxrungtham, Kiat
影响因子：
3.7
作者：
Briney BS;Willis JR;Crowe JE Jr
通讯作者：
Crowe JE Jr
影响因子：
14.9
作者：
Giudicelli, Veronique;Duroux, Patrice;Ginestoux, Chantal;Folch, Geraldine;Jabado-Michaloud, Joumana;Chaume, Denys;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
影响因子：
56.9
作者：
Gibbs, Richard A.;Rogers, Jeffrey;Zwieg, Ann S.
通讯作者：
Zwieg, Ann S.