Vaccine Preparation, Neutralizing Pattern And CryoEM Three Dimension Structure Of VLP Of Human Papillomavirus

High risk Human Papillomavirus (HPV) such as HPV16,18, 31, 33, 35, and 45 are associated with the development of the cervical cancer. HPV18, the second most common cause of cervical cancer is more frequently detected in adenocarcinoma and the incidence of which is increasing. So, effective vaccine against HPV 18 would greatly reduce cervical cancer incidence.In this study, a hight efficient HPV18 L1 prokaryotic expression system was established. HPV 18 L1 can be expressed in soluble form and keep native conformation.A easy sacel-up process to purify and assemble bacterially expressed HPV18 L1 was established too. And all the test items fuifiled the criterions of the Pharmacopoeia of PRC. And animal experiment data showed bacterially expressed HPV18 VLPs can induce high titer neutralizing antibodies , and be able to induce protective immunity to papillomavirus infectionIn the base of HPV18 VLPs vaccine, mabs to HPV18 were screened. Six neutralizing antibodies were identified, and 11A9, 3C3 were regarded as predominant antibody by blocking experiment. To investigate the neutralizing pattern and binding stites of 11A9, the structure of HPV18 VLPs was studies with CryoEM and the 11A9-HPV18 VLP complex was prepared for further CryoEM study.Anyway, in this study an effective HPV18 VLPs vaccine was prepared in a low-cost and easy scale-up manner. Two predominant neutraliziong antibodies were identified. The neutralizing mechanism of 11A9 was studied. All of these provided useful informations to HPV vaccine design.