Polyanhydride Nanovaccines Induce Germinal Center B Cell Formation and Sustained Serum Antibody Responses.
Polyanhydride Nanovaccines Induce Germinal Center B Cell Formation and Sustained Serum Antibody Responses.
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聚酐纳米疫苗可诱导生发中心 B 细胞形成和持续的血清抗体反应。
DOI：
10.1166/jbn.2016.2242
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发表时间：
2016
影响因子：
2.9
通讯作者：
Narasimhan,Balaji
中科院分区：
文献类型：
--
作者：
VelaRamirez,JuliaE;Tygrett,LorraineT;Hao,Jihua;Habte,HabtomH;Cho,MichaelW;Greenspan,NeilS;Waldschmidt,ThomasJ;Narasimhan,Balaji
与可溶性蛋白相比，可生物降解的聚合物纳米颗粒亚单位疫苗通过增强抗原提呈和诱导保护性免疫反应而显示出良好的特性。具体地说，基于聚酸酐纳米颗粒的疫苗(即纳米疫苗)已被证明能够成功地包裹和释放抗原，激活B和T细胞，并诱导抗体和细胞介导的针对各种免疫原的免疫。胸腺依赖抗体反应的特征之一是生发中心(GC)的形成和GC B细胞的产生，GC B细胞是T辅助细胞驱动的细胞反应的一部分。为了进一步了解纳米疫苗在诱导抗原特异性免疫应答中的作用，本研究对纳米疫苗诱导生发中心B细胞形成和同型转换的能力及其对血清抗体应答的影响进行了研究。以1，6-二(对羧基苯氧基)己烷和1，8-二(对羧基苯氧基)-3，6-二氧辛烷为基础的聚酸酐纳米疫苗用于皮下注射病毒抗原。比较了纳米疫苗诱导的GC-B细胞形成和血清抗体反应与明胶疫苗制剂诱导的抗体反应。结果表明，与明矾制剂相比，单剂聚酸酐纳米疫苗可形成强健的GCs和血清抗体。这归因于纳米疫苗提供的抗原的持续释放。多剂量给药可提高免疫后最高滴度和GC-B细胞数，进一步维持纳米疫苗诱导的免疫应答。这些研究为聚酸酐纳米疫苗的作用机制提供了基础信息。
Biodegradable polymeric nanoparticle-based subunit vaccines have shown promising characteristics by enhancing antigen presentation and inducing protective immune responses when compared with soluble protein. Specifically, polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have been shown to successfully encapsulate and release antigens, activate B and T cells, and induce both antibody- and cell-mediated immunity towards a variety of immunogens. One of the characteristics of strong thymus-dependent antibody responses is the formation of germinal centers (GC) and the generation of GC B cells, which is part of the T helper cell driven cellular response. In order to further understand the role of nanovaccines in the induction of antigen-specific immune responses, their ability to induce germinal center B cell formation and isotype switching and the effects thereof on serum antibody responses were investigated in these studies. Polyanhydride nanovaccines based on 1,6-bis( p-carboxyphenoxy)hexane and 1,8-bis( p-carboxyphenoxy)-3,6-dioxaoctane were used to subcutaneously administer a viral antigen. GC B cell formation and serum antibody responses induced by the nanovaccines were compared to that induced by alum-based vaccine formulations. It was demonstrated that a single dose of polyanhydride nanovaccines resulted in the formation of robust GCs and serum antibody in comparison to that induced by the alum-based formulation. This was attributed to the sustained release of antigen provided by the nanovaccines. When administered in a multiple dose regimen, the highest post-immunization titer and GC B cell number was enhanced, and the immune response induced by the nanovaccines was further sustained. These studies provide foundational information on the mechanism of action of polyanhydride nanovaccines.
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影响因子：
9.7
作者：
Torres, Maria P.;Wilson-Welder, Jennifer H.;Lopac, Senja K.;Phanse, Yashdeep;Carrillo-Conde, Brenda;Ramer-Tait, Amanda E.;Bellaire, Bryan H.;Wannemuehler, Michael J.;Narasimhan, Balaji
通讯作者：
Narasimhan, Balaji
影响因子：
3.8
作者：
Wilson-Welder JH;Torres MP;Kipper MJ;Mallapragada SK;Wannemuehler MJ;Narasimhan B
通讯作者：
Narasimhan B
影响因子：
9.7
作者：
Carrillo-Conde, Brenda;Schiltz, Elise;Narasimhan, Balaji
通讯作者：
Narasimhan, Balaji
DOI：
10.1002/jbm.b.32820
发表时间：
2013-01-01
影响因子：
3.4
作者：
Huntimer, Lucas;Welder, Jennifer H. Wilson;Ramer-Tait, Amanda E.
通讯作者：
Ramer-Tait, Amanda E.
影响因子：
2.7
作者：
Goodman, Jonathan T.;Ramirez, Julia E. Vela;Narasimhan, Balaji
通讯作者：
Narasimhan, Balaji