PDF(Pubmed)
Abstract：
Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of -19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.
摘要：
人类继续面临寨卡病毒的风险。尽管有关寨卡的研究取得了重大进展，缺乏疫苗或批准的治疗给医疗保健提供者带来了进一步的挑战.在这项研究中,我们开发了一种微粒寨卡疫苗，使用灭活的完整寨卡病毒作为抗原，可以通过鼻内（IN）免疫无痛施用。这些微粒(MP)使用由我们的实验室开发的双重乳液方法配制。我们探索了使用MPL-A®和Alhydrogel®作为佐剂的主要剂量和两次加强剂量疫苗接种策略，以进一步刺激免疫反应。MPL-A®诱导Th1介导的免疫应答,而Alhydrogel®(明矾)诱导Th2介导的免疫应答。国会议员的回收率很高，尺寸小于5微米，和-19.42±0.66mV的粒子电荷。ZikaMP疫苗和佐剂ZikaMP疫苗的IN免疫显示出几种抗体（IgA，IgM,和IgG）和几种IgG亚型（IgG1，IgG2a，和IgG3）。疫苗MP引起平衡的Th1-和Th2-介导的免疫应答。免疫器官,比如脾脏和淋巴结，在两个疫苗组中，CD4辅助细胞和CD8细胞毒性T细胞反应均显着增加。ZikaMP疫苗和佐剂ZikaMP疫苗在脾脏和淋巴结中显示出强大的记忆反应（CD27和CD45R）。与无佐剂疫苗相比，佐剂疫苗诱导的寨卡病毒特异性细胞内细胞因子更高。我们的结果表明，可能需要一个以上的剂量或多个剂量来实现必要的免疫反应。与未接种疫苗的小鼠相比，通过鼻内途径给药时，寨卡疫苗MP和佐剂化MP疫苗表现出强大的体液，细胞，和记忆反应。在这项临床前研究中，我们建立了一种无痛的微粒寨卡疫苗,该疫苗在鼻内给药时产生显著的免疫反应.
