Novartis Vaccines, Cambridge, MA 02139, United States.
Vaccine. 2013 Aug 20;31(37):3872-8. doi: 10.1016/j.vaccine.2013.06.062. Epub 2013 Jul 2.
Parvovirus B19 is the causative agent of fifth disease in children, aplastic crisis in those with blood dyscrasias, and hydrops fetalis. Previous parvovirus B19 virus-like-particle (VLP) vaccine candidates were produced by co-infection of insect cells with two baculoviruses, one expressing wild-type VP1 and the other expressing VP2. In humans, the VLPs were immunogenic but reactogenic. We have developed new VLP-based parvovirus B19 vaccine candidates, produced by co-expressing VP2 and either wild-type VP1 or phospholipase-negative VP1 in a regulated ratio from a single plasmid in Saccharomyces cerevisiae. These VLPs are expressed efficiently, are very homogeneous, and can be highly purified. Although VP2 alone can form VLPs, in mouse immunizations, VP1 and the adjuvant MF59 are required to elicit a neutralizing response. Wild-type VLPs and those with phospholipase-negative VP1 are equivalently potent. The purity, homogeneity, yeast origin, and lack of phospholipase activity of these VLPs address potential causes of previously observed reactogenicity.
细小病毒 B19 是儿童第五病的病原体，也是血液疾病患者再生障碍危象和胎儿水肿的病原体。以前的细小病毒 B19 病毒样颗粒（VLP）疫苗候选物是通过两种杆状病毒共感染昆虫细胞产生的，一种表达野生型 VP1，另一种表达 VP2。在人类中，VLPs 具有免疫原性，但具有反应原性。我们已经开发了新的基于 VLP 的细小病毒 B19 疫苗候选物，通过在酿酒酵母中从单个质粒中以受调控的比例共表达 VP2 和野生型 VP1 或磷脂酶阴性 VP1 来生产。这些 VLP 表达效率高，非常均一，并且可以高度纯化。尽管 VP2 可以单独形成 VLPs，但在小鼠免疫中，需要 VP1 和佐剂 MF59 来引发中和反应。野生型 VLPs 和具有磷脂酶阴性 VP1 的 VLPs 同样有效。这些 VLPs 的纯度、均一性、酵母来源和缺乏磷脂酶活性解决了以前观察到的反应原性的潜在原因。
