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

Abstract

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, these findings 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. Keywords Zika virus (ZIKV) Á Envelope protein Á Baculovirus Á Immunogenicity Á Neutralizing antibody Á Viral challenge Dan Luo and Yuanjiu Miao have contributed equally to this work.

Solutions against emerging infectious and noninfectious human diseases through the application of baculovirus technologies

“…Recently, a report described for the first time the display of the E protein on the BV surface and the resulting immunogenic and protective effect against ZIKV. To the display, E was fused with the signal peptide and the transmembrane domain from AcMNPV GP64 (Luo et al 2020). For the purpose of ZIKV diagnosis, the nonstructural proteins NS1 and E from the ZIKV were efficiently produced in insect cells infected with rec-baculoviruses.…”

Baculovirus displaying SARS-CoV-2 spike RBD promotes neutralizing antibody production in a mouse model

“…Microneutralization assay of baculovirus displaying VP1 of Human Enterovirus 71 gave 1:32 to 1:64; however, mice were injected subcutaneously with a lower dose of 108 PFU but with Freund's adjuvant [54]. The display of Zika virus envelope protein on baculovirus with Freund's adjuvant after three doses gave PRNT50 = 1:47.76 after 15μg/dose intraperitoneal injection in mice [61]. These data indicate that our system can elicit comparable neutralizing antibodies compared to other displayed proteins on baculovirus displayed antigen.…”

Vaccination with a Zika virus envelope domain III protein induces neutralizing antibodies and partial protection against Asian genotype in immunocompetent mice

“…For example, a subunit vaccine composed of protein fragments can induce toxic immune responses and the pre-existing immunity to viral vector can suppress vaccine efficacy [ 39 ]. Moreover, potential tumorigenesis elicited by the insertion of a gene into a DNA or mRNA vaccine [ 40 , 41 ], as well as unexpected immune response by viral-vectored vaccines [ 24 , 42 ], can be risk factors. Lately, subunit vaccines utilizing ZIKV EDIII region to provide safety and efficacy has being developed and they protected hosts from ZIKV challenge [ 16 , 21 , 43 ].…”