Liu Ying, Wen Zhiyuan, Carrion Ricardo, Nunneley Jerritt, Staples Hilary, Ticer Anysha, Patterson Jean L, Compans Richard W, Ye Ling, Yang Chinglai
State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Department of Microbiology and Immunology and Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, United States.
Front Microbiol. 2020 Feb 27;11:304. doi: 10.3389/fmicb.2020.00304. eCollection 2020.
Ebolavirus (EBOV) infection in humans causes severe hemorrhagic fevers with high mortality rates that range from 30 to 80% as shown in different outbreaks. Thus the development of safe and efficacious EBOV vaccines remains an important goal for biomedical research. We have shown in early studies that immunization with insect cell-produced EBOV virus-like particles (VLPs) is able to induce protect vaccinated mice against lethal EBOV challenge. In the present study, we investigated immune responses induced by Ebola VLPs via two different routes, intramuscular and intradermal immunizations, in guinea pigs. Analyses of antibody responses revealed that similar levels of total IgG antibodies against the EBOV glycoprotein (GP) were induced by the two different immunization methods. However, further characterization showed that the EBOV GP-specific antibodies induced by intramuscular immunization were mainly of the IgG2 subtype whereas both IgG1 and IgG2 antibodies against EBOV GP were induced by intradermal immunization. In contrast, antibody responses against the EBOV matrix protein VP40 induced by intramuscular or intradermal immunizations exhibited similar IgG1 and IgG2 profiles. More interestingly, we found that the sites that the IgG1 antibodies induced by intradermal immunizations bind to in GP are different from those that bind to the IgG2 antibodies induced by intramuscular immunization. Further analyses revealed that sera from all vaccinated guinea pigs exhibited neutralizing activity against Ebola GP-mediated HIV pseudovirion infection at high levels. Moreover, all EBOV VLP-vaccinated guinea pigs survived the challenge by a high dose (1000 pfu) of guinea pig-adapted EBOV, while all control guinea pigs immunized with irrelevant VLPs succumbed to the challenge. The induction of both IgG1 and IgG2 antibody responses that recognized broader sites in GP by intradermal immunization of EBOV VLPs indicates that this approach may represent a more advantageous route of vaccination against virus infection.
埃博拉病毒（EBOV）感染人类会引发严重出血热，致死率很高，在不同疫情中死亡率在30%至80%之间。因此，研发安全有效的EBOV疫苗仍是生物医学研究的一个重要目标。我们在早期研究中表明，用昆虫细胞生产的EBOV病毒样颗粒（VLP）进行免疫能够诱导保护接种疫苗的小鼠抵御致死性EBOV攻击。在本研究中，我们在豚鼠中通过肌肉注射和皮内注射两种不同途径研究了埃博拉VLP诱导的免疫反应。抗体反应分析显示，两种不同免疫方法诱导出的针对EBOV糖蛋白（GP）的总IgG抗体水平相似。然而，进一步的特性分析表明，肌肉注射诱导的EBOV GP特异性抗体主要是IgG2亚型，而皮内注射诱导出了针对EBOV GP的IgG1和IgG2抗体。相比之下，肌肉注射或皮内注射诱导的针对EBOV基质蛋白VP40的抗体反应呈现出相似的IgG1和IgG2谱型。更有趣的是，我们发现皮内注射诱导的IgG1抗体在GP上的结合位点与肌肉注射诱导的IgG2抗体的结合位点不同。进一步分析显示，所有接种疫苗的豚鼠血清对埃博拉GP介导的HIV假病毒感染均表现出高水平的中和活性。此外，所有接种EBOV VLP的豚鼠在接受高剂量（1000 pfu）豚鼠适应型EBOV攻击后存活下来，而所有用无关VLP免疫的对照豚鼠均死于攻击。通过皮内注射EBOV VLP诱导出能识别GP中更广泛位点的IgG1和IgG2抗体反应，表明这种方法可能是针对病毒感染的一种更具优势的疫苗接种途径。
