Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge.
Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge.
复制标题
DOI：
10.1016/j.xcrm.2022.100658
复制
发表时间：
2022-06-21
影响因子：
14.3
通讯作者：
McGuire, Andrew T.
中科院分区：
文献类型：
--
作者：
Malhi, Harman;Homad, Leah J.;Wan, Yu-Hsin;Poudel, Bibhav;Fiala, Brooke;Borst, Andrew J.;Wang, Jing Yang;Walkey, Carl;Price, Jason;Wall, Abigail;Singh, Suruchi;Moodie, Zoe;Carter, Lauren;Handa, Simran;Correnti, Colin E.;Stoddard, Barry L.;Veesler, David;Pancera, Marie;Olson, James;King, Neil P.;McGuire, Andrew T.
爱泼斯坦-巴尔病毒（EBV）是一种与癌症相关的病原体，每年导致16.5万人死亡。EBV也是传染性单核细胞增多症的病原，与多发性硬化症和类风湿性关节炎有关。因此，EBV疫苗将对全球健康产生重大影响。EBV经口传播，对上皮细胞和B细胞有趋向性。因此，需要一种疫苗来防止这两种病毒在口腔内的感染。针对gH/gL糖蛋白复合物的单克隆抗体被动转移可预防人源化小鼠和恒河猴的实验性EBV感染，这表明gH/gL是一种有吸引力的候选疫苗。在这里，我们评估了几种gH/gL纳米颗粒疫苗的免疫原性。与单体gH/gL相比，它们均表现出优越的免疫原性。在人源化小鼠中，显示60个gH/gL拷贝的纳米颗粒可引发抗体，保护小鼠免受致命的EBV攻击，而单个gH/gL所引发的抗体则不能。这些数据激励了EBV的gH/gL纳米颗粒疫苗的进一步开发。纳米颗粒诱导的抗体可保护人源化小鼠免受EBV致命攻击。EBV是一种癌症相关病原体，目前尚无疫苗。在这里，Malhi等人开发了纳米颗粒，显示病毒gH/gL糖蛋白复合物，可引发有效的中和抗体反应，能够保护人源化小鼠免受致命的EBV攻击。这些结果支持将gH/gL纳米颗粒用于EBV疫苗开发。
Epstein-Barr virus (EBV) is a cancer-associated pathogen responsible for 165,000 deaths annually. EBV is also the etiological agent of infectious mononucleosis and is linked to multiple sclerosis and rheumatoid arthritis. Thus, an EBV vaccine would have a significant global health impact. EBV is orally transmitted and has tropism for epithelial and B cells. Therefore, a vaccine would need to prevent infection of both in the oral cavity. Passive transfer of monoclonal antibodies against the gH/gL glycoprotein complex prevent experimental EBV infection in humanized mice and rhesus macaques, suggesting that gH/gL is an attractive vaccine candidate. Here, we evaluate the immunogenicity of several gH/gL nanoparticle vaccines. All display superior immunogenicity relative to monomeric gH/gL. A nanoparticle displaying 60 copies of gH/gL elicits antibodies that protect against lethal EBV challenge in humanized mice, whereas antibodies elicited by monomeric gH/gL do not. These data motivate further development of gH/gL nanoparticle vaccines for EBV. Design of several self-assembling nanoparticles displaying EBV gH/gL Demonstrate multivalent display of gH/gL results in superior immunogenicity in mice Nanoparticle-elicited antibodies protect humanized mice against lethal EBV challenge EBV is a cancer-associated pathogen for which there is no vaccine. Here, Malhi et al. develop nanoparticles displaying the viral gH/gL glycoprotein complex that elicit potent neutralizing antibody responses capable of protecting against lethal EBV challenge in humanized mice. These results support the use of gH/gL nanoparticles for EBV vaccine development.
登录
查看更多内容
影响因子：
6.7
作者：
Angelini DF;Serafini B;Piras E;Severa M;Coccia EM;Rosicarelli B;Ruggieri S;Gasperini C;Buttari F;Centonze D;Mechelli R;Salvetti M;Borsellino G;Aloisi F;Battistini L
通讯作者：
Battistini L
DOI：
10.1073/pnas.0907508106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Chesnokova, Liudmila S.;Nishimura, Stephen L.;Hutt-Fletcher, Lindsey M.
通讯作者：
Hutt-Fletcher, Lindsey M.
DOI：
10.1126/science.abm3425
发表时间：
2022-01-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Cohen JI
通讯作者：
Cohen JI
影响因子：
5.5
作者：
Cohen, Jeffrey I.;Mocarski, Edward S.;Raab-Traub, Nancy;Corey, Lawrence;Nabel, Gary J.
通讯作者：
Nabel, Gary J.