Modified mRNA Vaccines Protect against Zika Virus infection

Justin M. Richner, Sunny Himansu, Kimberly A. Dowd, Scott L. Butler, Vanessa Salazar, Julie M. Fox, Justin G. Julander, William W. Tang, Sujan Shresta, Theodore C. Pierson, Giuseppe Ciaramella, Michael S. Diamond

Cell. 2017 Mar 9; 168(6):1114-1125.

Speaker: Hong-Jyun Huang(黃鴻鈞)           Time: 14:00~15:00, Dec. 27, 2017

Commentator: Dr. Ai-Li Shiau (蕭璦莉 教授)   Place: Room 601

Abstract:

  Zika virus (ZIKV) has been reported as a highly concerned global disease of many countries in Americas, Africa, and Asia. As it spreads, more severe clinical consequences has been observed. Moreover, it can transmit from mosquito bites, pregnancy mother to child, sex, and blood transfusion, which may cause cerebral calcifications, microcephaly, and miscarriage in fetuses during pregnancy, and cause Guillain-Barré syndrome (GBS) in adults. However, there is no specific medicine or vaccine for ZIKV. In order to develop a vaccine for ZIKV, the authors designed a modified mRNA combined the signal sequence from human IgE and the full length prM and E gene from ZIKV, packaged into lipid nanoparticles (IgE_sig-prM-E LNPs). The LNP vaccine can provide protection in AG129 and C57BL/6 mice challenged with ZIKV as determined by serum neutralization, EC50, survival rate, and body weights in vivo. To minimize the antibody-dependent enhancement (ADE) caused by the LNP vaccine, the authors engineered four mutations in or near the E protein Domain II. Also, they replaced the IgE leader sequence with Japanese encephalitis virus (JEV_sig) to increase the efficiency of host signalase cleavage. The full length (FL) mutant ZIKV vaccine induced neutralizing antibody responses in non-pregnant female BALB/c mice that protected against virus dissemination in uterus and brain in vivo. Moreover, the FL mutant ZIKV vaccines induced serum antibody responses that resulted in less ADE of DENV-1 infection in cell culture and immune enhancement of DENV-2 infection in AG129 mice. In summary, the modified mRNA vaccine encapsulated into LNPs can be a candidate vaccine for ZIKV infection.

Reference:

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