Gonzaga Zennia Jean C, Merakou Christina, DiGiandomenico Antonio, Priebe Gregory P, Rehm Bernd H A
Centre for Cell Factories and Biopolymers (CCFB), Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, QLD 4111, Australia.
Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Vaccines (Basel). 2021 Jul 20;9(7):803. doi: 10.3390/vaccines9070803.
Despite numerous efforts to develop an effective vaccine against , no vaccine has yet been approved for human use. This study investigates the utility of the inherently produced polyhydroxyalkanaote (PHA) inclusions and associated host-cell proteins (HCP) as a particulate vaccine platform. We further engineered PHA inclusions to display epitopes derived from the outer membrane proteins OprF/OprI/AlgE (Ag) or the type III secretion system translocator PopB. PHA and engineered PHA beads induced antigen-specific humoral, cell-mediated immune responses, anti-HCP and anti-polysaccharide Psl responses in mice. Antibodies mediated opsonophagocytic killing and serotype-independent protective immunity as shown by 100% survival upon challenge with in an acute pneumonia murine model. Vaccines were stable at 4 °C for at least one year. Overall, our data suggest that vaccination with subcellular empty PHA beads was sufficient to elicit multiple immune effectors that can prevent infection.
尽管为研发一种有效的抗[病原体名称]疫苗付出了诸多努力，但尚无疫苗获批用于人类。本研究调查了[病原体名称]天然产生的聚羟基链烷酸酯（PHA）包涵体及相关宿主细胞蛋白（HCP）作为颗粒疫苗平台的效用。我们进一步对PHA包涵体进行工程改造，使其展示源自外膜蛋白OprF/OprI/AlgE（Ag）或III型分泌系统转运蛋白PopB的表位。PHA和工程化PHA珠在小鼠中诱导了抗原特异性体液免疫、细胞介导的免疫反应、抗HCP和抗多糖Psl反应。抗体介导调理吞噬杀伤作用以及血清型非依赖性保护性免疫，如在急性肺炎小鼠模型中经[病原体名称]攻击后100%存活所示。疫苗在4℃下至少稳定一年。总体而言，我们的数据表明，用亚细胞空PHA珠进行疫苗接种足以引发多种免疫效应物，从而预防[病原体名称]感染。
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