Micro-nano Platforms for HSV Vaccine

描述（由申请人提供）：2型单纯疱疹病毒（HSV-2）是一种常见的病原体，其血清阳性率在过去几年中在美国一直在上升。目前还没有针对这种病毒的疫苗或有效的杀菌剂。除了与导致生殖器溃疡的有症状疾病相关的不适外，无症状脱落大大增强了病毒在人与人之间的传播。2型单纯疱疹病毒还使对人类免疫缺陷病毒（HIV）的易感性提高2-3倍。因此，迫切需要一种强效杀菌剂和有效的疫苗。在这个提议中，我们计划探索开发一种独特的非侵入性粘膜杀菌剂/疫苗组合的想法，该组合最初通过有效捕获HSV-2病毒粒子并使其无感染性来发挥杀菌剂的作用，然后为粘膜抗原呈递细胞提供一个独特的病毒抗原展示平台，用于加工、呈递和诱导免疫。这种新颖的平台是基于我们独特设计的氧化锌微纳刺突颗粒（ZnO-MNPs），它可以非常高效地捕获HSV病毒粒子。这种诱捕将病毒粒子集中在一个地方，使它们无法进入细胞。我们提出，在ZnO- mnps上高浓度捕获的病毒粒子将引起非常强的免疫反应，而不需要任何额外的佐剂，因为ZnO已经显示出良好的佐剂特性。我们的杀菌剂/疫苗组合的另一个额外优势是氧化锌已经在普通化妆品中使用。提出了两个探索目标。目的1将验证ZnO-MNPs可以作为一种有效的杀微生物剂，通过在体内阻止病毒附着在宿主细胞上的假设。目的2将验证被ZnO-MNPs捕获的HSV-2病毒粒子可以被粘膜抗原呈递细胞识别并加工以促进免疫发育的假设。总的来说，我们期望证明一种新的病毒抑制平台的疫苗功效，这将对预防HSV-2和许多其他病毒性疾病具有路径定义意义。

DESCRIPTION (provided by applicant): Herpes simplex virus type-2 (HSV-2) is a common pathogen with a seroprevalence rate that has been increasing in the US over the last several years. There is no vaccine or effective microbicide available against the virus. Apart from the discomfort associated with the symptomatic disease which results in genital ulcers, asymptomatic shedding greatly enhances person-to-person virus transmission. HSV-2 also enhances susceptibility to human immunodeficiency virus (HIV) by 2-3 folds. Therefore, there is an urgent need for a strong microbicide and an effective vaccine. In this proposal we plan to explore the idea of developing a unique non-invasive mucosal microbicide/vaccine combo which initially functions as a microbicide by effectively trapping HSV-2 virions and rendering them non-infective and then provides a unique viral antigen displaying platform for the mucosal antigen presenting cells for processing, presentation, and induction of immunity. This novel platform is based on our uniquely designed zinc oxide micro-nano spike particles (ZnO-MNPs), which trap HSV virions with very high efficacy. The trapping, which concentrates the virions at one place, renders them unable to enter cells. We propose that high concentrations of trapped virions on ZnO-MNPs will elicit a very strong immune response without the need of any additional adjuvant, since ZnO is already shown to have good adjuvant properties. Another added advantage of our microbicide/vaccine combo is that Zinc oxide is already used in common cosmetic products. Two exploratory Aims are proposed. Aim 1 will test the hypothesis that ZnO-MNPs can act as an effective microbicide by preventing virus attachment to host cells in vivo. Aim 2 will test the hypothesis that HSV-2 virions trapped by ZnO-MNPs can be recognized by mucosal antigen presenting cells and processed for immunity development. Overall, we expect to prove the vaccine efficacy of a new virostatic platform, which will have path defining implications for protection against HSV-2 and many additional viral diseases.