- 作者: Li-Chen Yen, Hsin-Wei Chen, Chia-Lo Ho, Chang-Chi Lin, Yi-Ling Lin, Qiao-Wen Yang, Kuo-Chou Chiu, Shu-Pei Lien, Ren-Jye Lin & Ching-Len Liao
- 作者服務機構: 1.Department of Family Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 2.Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan 3.Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 4.Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan 5.Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan 6.National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, No. 35, Keyan Road, Zhunan, Miaoli County, 35053, Taiwan 7.National Mosquito-Borne Diseases Control Research Center, National Health Research Institute, Miaoli, Taiwan 8.School of Dentistry, National Defense Medical Center, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
Background Flavivirus causes many serious public health problems worldwide. However, licensed DENV vaccine has
restrictions on its use, and there is currently no approved ZIKV vaccine. Development of a potent and safe favivirus
vaccine is urgently needed. As a previous study revealed the epitope, RCPTQGE, located on the bc loop in the E
protein domain II of DENV, in this study, we rationally designed and synthesized a series of peptides based on the
sequence of JEV epitope RCPTTGE and DENV/ZIKV epitope RCPTQGE.
Methods Immune sera were generated by immunization with the peptides which were synthesized by using fve
copies of RCPTTGE or RCPTQGE and named as JEV-NTE and DV/ZV-NTE.
Immunogenicity and neutralizing abilities of
JEV-NTE or DV/ZV-NTE-immune sera against favivirus were evaluated by ELISA and neutralization tests, respectively.
Protective efcacy in vivo were determined by passive transfer the immune sera into JEV-infected ICR or DENV- and
ZIKV-challenged AG129 mice. In vitro and in vivo ADE assays were used to examine whether JEV-NTE or DV/ZV-NTEimmune sera would induce ADE.
Results Passive immunization with JEV-NTE-immunized sera or DV/ZV-NTE-immunized sera could increase the
survival rate or prolong the survival time in JEV-challenged ICR mice and reduce the viremia levels signifcantly in
DENV- or ZIKV-infected AG129 mice. Furthermore, neither JEV -NTE- nor DV/ZV-NTE-immune sera induced antibodydependent enhancement (ADE) as compared with the control mAb 4G2 both in vitro and in vivo.
Conclusions We showed for the frst time that novel bc loop epitope RCPTQGE located on the amino acids 73 to 79
of DENV/ZIKV E protein could elicit cross-neutralizing antibodies and reduced the viremia level in DENV- and ZIKVchallenged AG129 mice. Our results highlighted that the bc loop epitope could be a promising target for favivirus
vaccine development. - 中文關鍵字:
- 英文關鍵字: Japanese encephalitis virus, Dengue virus, Zika virus, Flavivirus vaccine, Neutralizing epitope, Envelop protein domain II