Wu Xilin, Ma Xiaohua, Li Yanlei, Xu Yue, Zheng Nan, Xu Shijie, Nawaz Waqas, Wu Zhiwei
Center for Public Health Research, Medical School, Nanjing University, Nanjing, PR, China.
State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, PR, China.
Antib Ther. 2019 Mar 4;2(2):45-53. doi: 10.1093/abt/tbz004. eCollection 2019 Apr.
Cervical cancer caused by human papillomavirus (HPV) infections is one of the most common cancers affecting women worldwide. Current preventative HPV vaccines on the market are composed of HPV L1 protein produced either in the yeast such as Gardasil or in the insect cells such as Cervarix. The duration of efficacy and cross-protection remain highly desirable for the improvement of current prophylactic HPV vaccine. Given that HPV carries out infection and replicates in mammalian cells, L2 protein, which is not included in the current licensed vaccines, is included in the third generation of HPV vaccine in pursuing of providing broader prevention. We hypothesize that a virus-like particle (VLP) consisting of HPV L1 plus L2 proteins generated in mammalian cells will present conformations more closely to native HPV, thus it will provide more durable and broader efficacy of prevention.
We took advantage of 293TT cells to produce VLP containing L1 and L2 proteins of HPV16 and HPV18, respectively.
VLP particles of uniformed size and morphology were observed, and potent and broadly neutralizing antibodies were induced in mice and rabbits. In addition, compared to bivalent HPV vaccine of Cervarix, our HPV L1-L2 VLPs elicited higher titer of anti-sera, and the anti-sera also presented comparable neutralization potency against HPV16 and HPV18 infections even a much less potent adjuvant was used in our case.
Our VLPs were capable of eliciting stronger and more broadly neutralizing activities against various HPV subtypes and were potential candidate HPV vaccines.
人乳头瘤病毒（HPV）感染引起的宫颈癌是全球影响女性的最常见癌症之一。目前市场上的预防性HPV疫苗由在酵母（如佳达修）或昆虫细胞（如卉妍康）中产生的HPV L1蛋白组成。对于当前预防性HPV疫苗的改进而言，疗效持续时间和交叉保护仍然是非常令人期待的。鉴于HPV在哺乳动物细胞中进行感染和复制，在第三代HPV疫苗中纳入了目前已获许可疫苗中未包含的L2蛋白，以寻求提供更广泛的预防效果。我们假设，由在哺乳动物细胞中产生的HPV L1加L2蛋白组成的病毒样颗粒（VLP）将呈现与天然HPV更接近的构象，因此它将提供更持久和更广泛的预防效果。
我们利用293TT细胞分别生产含有HPV16和HPV18的L1和L2蛋白的VLP。
观察到大小和形态均一的VLP颗粒，并且在小鼠和兔子中诱导产生了强效且具有广泛中和作用的抗体。此外，与卉妍康二价HPV疫苗相比，我们的HPV L1-L2 VLP诱导产生了更高滴度的抗血清，并且即使在我们的实验中使用了效力低得多的佐剂，该抗血清对HPV16和HPV18感染也表现出相当的中和效力。
我们的VLP能够针对各种HPV亚型引发更强且更具广泛中和作用的活性，是HPV疫苗的潜在候选物。
