MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, People's Republic of China; Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang 050017, Heibei Province, People's Republic of China.
Capital Medical University Affiliated Beijing You'an Hospital, Beijing Institute of Hepatology, Beijing 100069, People's Republic of China.
Vaccine. 2018 Jun 18;36(26):3740-3746. doi: 10.1016/j.vaccine.2018.05.061. Epub 2018 May 16.
Therapeutic vaccines represent a unique approach to hepatitis B virus (HBV) treatment and have the potential to induce long-term control of infection. This study explored the immune responses of rhesus macaques to novel vaccines comprising the S, PreS1, and Core antigens of the HBV that showed promise as prophylactic and therapeutic approaches in a mouse model. The tested vaccines included two DNA vaccines (pVRC-SS1, pVRC-CS1), an HBV particle subunit (HBSS1) vaccine and the recombinant vaccinia virus- (RVJ-) based vaccines (RVJSS1 and RVJCS1) in which SS1 containing S (1-223 aa) and PreS1 (21-47 aa), CS1 containing Core (1-144 aa) and PreS1 (1-42 aa). The humoral immunity and cell-mediated immunity (CMI) induced by vaccines comprising the S, PreS1, and Core antigens of HBV were investigated in a longitudinal study that continued up to 98 weeks after the firstvaccination. In rhesus macaques, anti-PreS1 antibody was induced more rapidly than anti-S or anti-Core antibody after DNA vaccination. The antibody and cell-mediated immune responses against S, PreS1, and C were significantly enhanced in macaques boosted with RVJSS1 and RVJCS1, whereas the cell-mediated response to C was most robust and durable. The immune response to S, PreS1, and C was restored by HBSS1 boosting and detected in macaques until weeks 74 and 98 after the first vaccination. Additionally, robust neutralizing activity was detected at week 52. In conclusion, novel HBV vaccine candidates, especially those used for therapeutic applications should incorporate the PreS1 and Core antigens.
治疗性疫苗代表了乙型肝炎病毒（HBV）治疗的一种独特方法，具有诱导感染长期控制的潜力。本研究探索了新型疫苗在恒河猴中的免疫反应，这些疫苗包含 HBV 的 S、PreS1 和 Core 抗原，在小鼠模型中表现出作为预防和治疗方法的潜力。测试的疫苗包括两种 DNA 疫苗（pVRC-SS1、pVRC-CS1）、一种 HBV 颗粒亚单位（HBSS1）疫苗和基于重组痘苗病毒的疫苗（RVJSS1 和 RVJCS1），其中 SS1 包含 S（1-223 aa）和 PreS1（21-47 aa），CS1 包含 Core（1-144 aa）和 PreS1（1-42 aa）。在首次接种后长达 98 周的纵向研究中，研究了包含 HBV 的 S、PreS1 和 Core 抗原的疫苗诱导的体液免疫和细胞介导免疫（CMI）。在恒河猴中，DNA 疫苗接种后，抗-PreS1 抗体的诱导速度快于抗-S 或抗-Core 抗体。用 RVJSS1 和 RVJCS1 加强免疫后，猴体内对 S、PreS1 和 C 的抗体和细胞介导免疫反应显著增强，而对 C 的细胞介导反应最为强烈和持久。HBSS1 加强免疫可恢复 S、PreS1 和 C 的免疫反应，并在首次接种后第 74 周和第 98 周检测到。此外，在第 52 周检测到了强大的中和活性。总之，新型 HBV 疫苗候选物，特别是那些用于治疗应用的疫苗，应包含 PreS1 和 Core 抗原。
