Braz Gomes Kimberly, D'Sa Sucheta, Allotey-Babington Grace Lovia, Kang Sang-Moo, D'Souza Martin J
Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, Mercer University, Atlanta, GA 30341, USA.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Vaccines (Basel). 2021 Nov 15;9(11):1324. doi: 10.3390/vaccines9111324.
In this study, our goal was to utilize the extracellular domain matrix-2 protein virus-like particle (M2e VLP) that has been found to be highly conserved amongst all strains of influenza and could serve as a potential vaccine candidate against influenza. Previous studies have demonstrated that the VLP of the M2e showed increased activation of innate and adaptive immune responses. Therefore, to further explore its level of efficacy and protection, this vaccine was administered transdermally and tested in a pre-clinical mouse model. The M2e VLP was encapsulated into a polymeric matrix with the addition of Alhydrogel and Monophosphoryl Lipid-A (MPL-A), together referred to as AS04. The M2e VLP formulations induced IgG titers, with increased levels of IgG1 in the M2e VLP MP groups and further elevated levels of IgG2a were found specifically in the M2e VLP MP Adjuvant group. This trend in humoral immunity was also observed from a cell-mediated standpoint, where M2e VLP MP groups showed increased expression in CD4 T cells in the spleen and the lymph node and high levels of CD8 T cells in the lymph node. Taken together, the results illustrate the immunogenic potential of the matrix-2 protein virus-like particle (M2e VLP) vaccine.
在本研究中,我们的目标是利用细胞外结构域基质-2蛋白病毒样颗粒(M2e VLP),该颗粒在所有流感毒株中高度保守,可作为一种潜在的流感疫苗候选物。先前的研究表明,M2e的VLP显示出先天免疫和适应性免疫反应的激活增加。因此,为了进一步探索其疗效和保护水平,该疫苗通过皮内给药,并在临床前小鼠模型中进行测试。M2e VLP与添加的氢氧化铝和单磷酰脂质A(MPL-A)一起封装在聚合物基质中,统称为AS04。M2e VLP制剂诱导了IgG滴度,M2e VLP MP组中IgG1水平升高,并且在M2e VLP MP佐剂组中特别发现IgG2a水平进一步升高。从细胞介导的角度也观察到了这种体液免疫趋势,其中M2e VLP MP组在脾脏和淋巴结中的CD4 T细胞表达增加,在淋巴结中的CD8 T细胞水平较高。综上所述,结果说明了基质-2蛋白病毒样颗粒(M2e VLP)疫苗的免疫原性潜力。