Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets.
Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets.
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DOI：
10.1080/19420862.2017.1386825
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发表时间：
2018-01
期刊：
影响因子：
5.3
通讯作者：
Leighton PA
中科院分区：
文献类型：
--
作者：
Ching KH;Collarini EJ;Abdiche YN;Bedinger D;Pedersen D;Izquierdo S;Harriman R;Zhu L;Etches RJ;van de Lavoir MC;Harriman WD;Leighton PA
用于发现人类单抗的转基因动物平台已经在小鼠、大鼠、兔子和奶牛身上开发出来。这些动物对人类蛋白质的免疫反应受到它们对哺乳动物保守表位的耐受性的限制。为了扩大可获得的表位范围，我们选择了一个与人类亲缘关系较小的动物宿主。具体地说，我们获得了表达免疫球蛋白重链和轻链基因座抗体的转基因鸡，这些基因座包含人可变区和鸡的恒定区。从这些禽类中，回收成对的人类轻链和重链可变区，并将其克隆为完全人类重组抗体。表达人类抗体的鸡表现出正常的B细胞发育，并提高对保守的人类蛋白的免疫反应，而这些蛋白在小鼠中不具有免疫原性。完全人类的单抗可以用亚纳摩尔亲和力回收。人类蛋白抗体的结合数据显示，表位覆盖率类似于野生型鸡，我们之前已经证明，这比啮齿动物免疫产生的表位覆盖率更广。
Transgenic animal platforms for the discovery of human monoclonal antibodies have been developed in mice, rats, rabbits and cows. The immune response to human proteins is limited in these animals by their tolerance to mammalian-conserved epitopes. To expand the range of epitopes that are accessible, we have chosen an animal host that is less phylogenetically related to humans. Specifically, we generated transgenic chickens expressing antibodies from immunoglobulin heavy and light chain loci containing human variable regions and chicken constant regions. From these birds, paired human light and heavy chain variable regions are recovered and cloned as fully human recombinant antibodies. The human antibody-expressing chickens exhibit normal B cell development and raise immune responses to conserved human proteins that are not immunogenic in mice. Fully human monoclonal antibodies can be recovered with sub-nanomolar affinities. Binning data of antibodies to a human protein show epitope coverage similar to wild type chickens, which we previously showed is broader than that produced from rodent immunizations.
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影响因子：
3.7
作者：
Dimitrov L;Pedersen D;Ching KH;Yi H;Collarini EJ;Izquierdo S;van de Lavoir MC;Leighton PA
通讯作者：
Leighton PA
影响因子：
10.5
作者：
MCCORMACK, WT;THOMPSON, CB
通讯作者：
THOMPSON, CB
影响因子：
2.2
作者：
Ma, Biao;Osborn, Michael J.;Brueggemann, Marianne
通讯作者：
Brueggemann, Marianne
影响因子：
5.3
作者：
Koenitzer, Jennifer D.;Pramanick, Shreya;Izquierdo, Shelley
通讯作者：
Izquierdo, Shelley
影响因子：
3
作者：
Leighton, Philip A.;Pedersen, Darlene;Ching, Kathryn;Collarini, Ellen J.;Izquierdo, Shelley;Jacob, Roy;van de Lavoir, Marie-Cecile
通讯作者：
van de Lavoir, Marie-Cecile