A trivalent gC2/gD2/gE2 vaccine for herpes simplex virus generates antibody responses that block immune evasion domains on gC2 better than natural infection
A trivalent gC2/gD2/gE2 vaccine for herpes simplex virus generates antibody responses that block immune evasion domains on gC2 better than natural infection
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DOI：
10.1016/j.vaccine.2018.11.076
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发表时间：
2019-01-21
期刊：
影响因子：
5.5
通讯作者：
Friedman, Harvey M.
中科院分区：
文献类型：
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作者：
Hook, Lauren M.;Awasthi, Sita;Friedman, Harvey M.
预防和治疗生殖器疱疹的疫苗是公共卫生的高度优先事项。我们的疫苗开发方法是专注于阻断由 2 型单纯疱疹病毒 (HSV-2) 糖蛋白 D (gD2) 介导的病毒进入，并通过分别阻断 HSV-2 糖蛋白 C (gC2) 和 E (gE2) 上的免疫逃避结构域来防止病毒逃避补体和抗体攻击。 HSV-2 gC2 和 gE2 在病毒颗粒包膜和受感染细胞表面表达，它们是结合并阻止其免疫逃避活动的抗体的潜在目标。我们证明，人类自然感染或豚鼠阴道内接种期间产生的抗体与 gC2 结合，但通常无法阻断该糖蛋白上的免疫逃避结构域。相比之下，用gC2亚基抗原和CpG和明矾作为佐剂对初次感染或先前感染HSV-2的豚鼠进行免疫，会产生阻断参与免疫逃避的结构域的抗体。这些结果表明，gC2 上的免疫逃避结构域在感染过程中是弱抗原，但当与佐剂一起用作疫苗免疫原时，这些抗原会产生阻断免疫逃避结构域的抗体。 (C) 2018 Elsevier Ltd. 保留所有权利。
Vaccines for prevention and treatment of genital herpes are high public health priorities. Our approach towards vaccine development is to focus on blocking virus entry mediated by herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) and to prevent the virus from evading complement and antibody attack by blocking the immune evasion domains on HSV-2 glycoproteins C (gC2) and E (gE2), respectively. HSV-2 gC2 and gE2 are expressed on the virion envelope and infected cell surface where they are potential targets of antibodies that bind and block their immune evasion activities. We demonstrate that antibodies produced during natural infection in humans or intravaginal inoculation in guinea pigs bind to gC2 but generally fail to block the immune evasion domains on this glycoprotein. In contrast, immunization of naive or previously HSV-2-infected guinea pigs with gC2 subunit antigen administered with CpG and alum as adjuvants produces antibodies that block domains involved in immune evasion. These results indicate that immune evasion domains on gC2 are weak antigens during infection, yet when used as vaccine immunogens with adjuvants the antigens produce antibodies that block immune evasion domains. (C) 2018 Elsevier Ltd. All rights reserved.