Ball Jordan P, Springer Michael J, Ni Yawei, Finger-Baker Isaac, Martinez Juan, Hahn Jessica, Suber John F, DiMarco Ashley V, Talton James D, Cobb Ronald R
Research and Development Department, Nanotherapeutics, Inc., Alachua, Florida, United States of America.
PLoS One. 2017 May 18;12(5):e0177310. doi: 10.1371/journal.pone.0177310. eCollection 2017.
The global health community is beginning to understand the burden of norovirus-associated disease, which has a significant impact in both developed and developing countries. Norovirus virus like particle (VLP)-based vaccines are currently under development and have been shown to elicit systemic and mucosal immune responses when delivered intranasally. In the present study, we describe the use of a dry powder formulation (GelVac™) with an in situ gelling polysaccharide (GelSite™) extracted from Aloe vera for nasal delivery of a bivalent vaccine formulation containing both GI and GII.4 norovirus VLPs. Dose-ranging studies were performed to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs and determine any antigenic interference. A dose-dependent increase in systemic and mucosal immunogenicity against each of the VLPs were observed as well as a boosting effect for each VLP after the second dosing. A total antigen dose of ≥50 μg of each GI and GII.4 VLPs was determined to be the maximally immunogenic dose in guinea pigs. The immunogenicity results of this bivalent formulation, taken together with previous work on monovalent GelVac™ norovirus vaccine formulation, provides a basis for future development of this norovirus VLP vaccine.
全球卫生界开始认识到诺如病毒相关疾病的负担，这种疾病在发达国家和发展中国家都有重大影响。基于诺如病毒病毒样颗粒（VLP）的疫苗目前正在研发中，并且已证明经鼻给药时可引发全身和黏膜免疫反应。在本研究中，我们描述了一种干粉制剂（GelVac™）的使用，该制剂含有从芦荟中提取的原位凝胶多糖（GelSite™），用于经鼻递送包含GI和GII.4诺如病毒VLP的二价疫苗制剂。进行了剂量范围研究，以根据豚鼠的全身和黏膜免疫反应确定最佳抗原剂量，并确定是否存在抗原干扰。观察到针对每种VLP的全身和黏膜免疫原性呈剂量依赖性增加，并且在第二次给药后每种VLP都有增强作用。确定每种GI和GII.4 VLP的总抗原剂量≥50μg为豚鼠中的最大免疫原性剂量。这种二价制剂的免疫原性结果，与先前关于单价GelVac™诺如病毒疫苗制剂的研究结果相结合，为这种诺如病毒VLP疫苗的未来开发提供了基础。
