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Vaccine and protective antibody: the development of interventions against Zika virus

Vaccine and protective antibody: the development of interven...

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第十三届全国免疫学学术大会

作者： Lianpan Dai Kun Xu Jian Song Fu Gao Beijing Institutes of Life Science Chinese Academy of Sciences Institute of Microbiology Chinese Academy of Sciences

The Zika virus(ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. ZIKV disease has spilled over into 84 countries and regions. So far, no prophylactics and therapeutics are available, therefore, countermeasure development is urgently demanded. Envelope protein mediated flavivirus adsorption and entry into host cells. therefore, it represents the major target for neutralizing antibodies and protective immunogen. We determined the crystal structure of envelope(E) protein of ZIKV, showing a typical type II viral fusion glycoprotein. Since the fusion loop(FL) of E protein is highly conserved among flaviviruses, we choose a FL-targeting broadly neutralizing antibody 2 A10 G6 for evaluation. 2 A10 G6 can partially protect lethal challenge of ZIKV infection. By analysis the structure of E in complexed with 2 A10 G6, we dissected the classic binding mode of FL-targeting *** chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low pre-existing immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7(AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E is sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed high neutralizing antibody titers within one week post-vaccination and the elicited antisera can cross-neutralize heterologous ZIKV strains. Impressively, one-dose inoculation of AdC7-M/E conferred mice sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against the ZIKV-induced testicular damage in mice model. These data demonstrate that AdC7-M/E is

关键词： Zika virus protective antibody antibody epitope Viral vector vaccine Zika vaccine

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