Baculovirus Surface Display of Zika Virus Envelope Protein Protects against Virus Challenge in Mouse Model

Zika virus(ZIKV)is emerging as a significant pathogen worldwide and may cause severe neurological disorders such as fetal microcephaly and Guillain-Barre syndrome.No drug or listed vaccines are currently available for preventing ZIKV infection.As a major target of neutralizing,ZIKV envelop(E)protein usually used for vaccine development.Nevertheless,the immunogenicity of ZIKV envelop(E)protein expressed by baculovirus display system has never been assessed.In this study,we reported a new strategy for surface display of ZIKV E protein by a recombinant baculovirus vector derived from Autographa californica multiple nuclear polyhedrosis virus(AcMNPV)and assessed its immunogenicity in mice.We produced recombinant fusion ZIKV E protein linked with signal peptide(SP)and transmembrane domain(TM)of AcMNPV GP64.The results showed that the recombinant protein was easy to produce by baculovirus display system.BALB/c mice immunized with this recombinant E protein developed ZIKV specific serum antibodies.The anti-E protein sera from the mice were able to effectively neutralize ZIKV in vitro.More importantly,AG6(IFN-a/b and IFN-c receptor deficient)mice immunized with recombinant E protein were protected against lethal ZIKV challenge.Together,thesefindings demonstrated that the recombinant E protein displayed by baculovirus can be conveniently prepared and displayed good immunogenicity in immunized mice.It is a promising practical approach for prompting the development of vaccine and related immunology research.

Recovery of a Far-Eastern Strain of Tick-Borne Encephalitis Virus with a Full-Length Infectious cDNA Clone

Tick-borne encephalitis virus(TBEV) is a pathogenic virus known to cause central nervous system(CNS) diseases in humans, and has become an increasing public health threat nowadays. The rates of TBEV infection in the endemic countries are increasing. However, there is no effective antiviral against the disease. This underscores the urgent need for tools to study the emergence and pathogenesis of TBEV and to accelerate the development of vaccines and antivirals. In this study, we reported an infectious c DNA clone of TBEV that was isolated in China(the WH2012 strain). A beta-globin intron was inserted in the coding region of nonstructural protein 1(NS1) gene to improve the stability of viral genome in bacteria. In mammalian cells, the inserted intron was excised and spliced precisely, which did not lead to the generation of inserted mutants. High titers of infectious progeny viruses were generated after the transfection of the infectious clone. The cDNA-derived TBEV replicated efficiently, and caused typical cytopathic effect(CPE) and plaques in BHK-21 cells. In addition, the CPE and growth curve of cDNA-derived virus were similar to that of its parental isolate in cells. Together, we have constructed the first infectious TBEV cDNA clone in China, and the clone can be used to investigate the genetic determinants of TBEV virulence and disease pathogenesis, and to develop countermeasures against the virus.