Abstract
Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research.
Highlights
Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates, with human fatality rates of up to 90% [1]
The purpose of expressing Sudan virus (SUDV) GP and VP40 proteins is to prepare anti-GP polyclonal antisera and anti-VP40 polyclonal antisera, and these two polyclonal antisera were successfully made through immunized mice with these two proteins twice respectively
The SUDV specific IgG antibodies and neutralizing antibodies were not detected in the virus-like particles (VLPs)-only group mice. These results demonstrate that SUDV VLPs at 20 μg antigen dose cannot stimulate the production of antibodies in mice, but this antigen dose mixed with ISA201 adjuvant can stimulate mice to produce specific IgG antibodies and neutralizing antibodies
Summary
Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates, with human fatality rates of up to 90% [1]. From these independent outbreaks, two distinct viruses were identified, Zaire Ebolavirus (EBOV) [2] and Sudan virus (SUDV) [3], which are members of the genus Ebolavirus and have been the cause of sporadic outbreaks in humans throughout the years [1]. EBOV, SUDV, Tai Forest Ebolavirus (TAFV), Bundibugyo Ebolavirus (BDBV), Reston Ebolavirus (RESTV) [4]. Both EBOV and SUDV are pathogenic to humans and nonhuman primates, causing severe hemorrhagic fever with high mortality rates of 67–90% [5,6]. Most of the cases were in Guinea, Liberia, and Sierra Leone, but some of them were imported into Europe and the United States (https://app.who.int/ebola/current-situation/ebola-situation-report-30-march-2016)
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