Hu Hui-Mei, Chen Hsin-Wei, Hsiao Yu-Ju, Wu Szu-Hsien, Chung Han-Hsuan, Hsieh Chun-Hsiang, Chong Pele, Leng Chih-Hsiang, Pan Chien-Hsiung
a National Institute of Infectious Disease and Vaccinology, National Health Research Institutes , Zhunan Town , Taiwan.
b Graduate Institute of Immunology, China Medical University , Taichung , Taiwan.
Hum Vaccin Immunother. 2016 Jul 2;12(7):1678-89. doi: 10.1080/21645515.2016.1143576. Epub 2016 Feb 22.
Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 ≥ 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3-specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine.
登革热对全球公共卫生有重大影响，而登革热疫苗的使用非常有限。在本研究中，我们评估了一种由表达登革热1至4型包膜蛋白结构域III（ED3）的重组麻疹病毒（MV）制成的登革热疫苗的免疫原性和保护效力。用MV载体登革热疫苗免疫后，小鼠产生了针对登革热病毒和MV的特异性干扰素-γ和抗体反应。还诱导产生了针对MV和登革热病毒的中和抗体，并且在MV载体登革热疫苗免疫的小鼠中检测到针对4种登革热病毒血清型的FRNT50≥10的保护水平。此外，在预先感染MV的小鼠中，MV载体登革热疫苗仍能诱导对登革热病毒的特异性干扰素-γ和抗体反应。这一发现表明，预先存在的对MV的免疫力并未阻断免疫反应的启动。相比之下，预先感染登革热3型的小鼠在对MV和登革热病毒的抗体反应方面没有影响，但观察到了占主导地位的登革热3型特异性T细胞反应。注射登革热2型后，与载体对照相比，在MV载体登革热疫苗免疫的小鼠中观察到可检测到但明显较低的病毒血症以及更高滴度的抗登革热2型中和抗体，这表明引发了能提供部分针对登革热2型保护作用的回忆性抗体反应。我们关于T细胞反应以及预先免疫MV或登革热病毒的影响的结果为MV载体登革热疫苗的未来应用提供了线索。
