Cross-Protection Conferred by Filovirus Virus-Like Particles Containing Trimeric Hybrid Glycoprotein

Abstract

Filoviruses are causative agents of hemorrhagic fever, and to date no effective vaccine or therapeutic has been approved to combat infection. Filovirus glycoprotein (GP) is the critical immunogenic component of filovirus vaccines, eliciting high levels of antibody after successful vaccination. Previous work has shown that protection against both Ebola virus (EBOV) and Marburg virus (MARV) can be achieved by vaccinating with a mixture of virus-like particles (VLPs) expressing either EBOV GP or MARV GP. In this study, the potential for eliciting effective immune responses against EBOV, Sudan virus, and MARV with a single GP construct was tested. Trimeric hybrid GPs were produced that expressed the sequence of Marburg GP2 in conjunction with a hybrid GP1 composed EBOV and Sudan virus GP sequences. VLPs expressing these constructs, along with EBOV VP40, provided comparable protection against MARV challenge, resulting in 75 or 100% protection. Protection from EBOV challenge differed depending upon the hybrid used, however, with one conferring 75% protection and one conferring no protection. By comparing the overall antibody titers and the neutralizing antibody titers specific for each virus, it is shown that higher antibody responses were elicited by the C terminal region of GP1 than by the N terminal region, and this correlated with protection. These data collectively suggest that GP2 and the C terminal region of GP1 are highly immunogenic, and they advance progress toward the development of a pan-filovirus vaccine.

An Exosome‐Based Vaccine Platform Imparts Cytotoxic T Lymphocyte Immunity Against Viral Antigens

“…The most potent CTL specific activation appeared to be that induced by EboV‐VP40 expressing DNA. However, it should be considered that VP40, even when fused with a foreign protein, maintains its ability to form VLPs, which are per se immunogenic . Hence, at least part of the CTL activity we detected would likely relate to the immune stimulation driven by EboV VLPs.…”

Quantitative Analysis of Repertoire-Scale Immunoglobulin Properties in Vaccine-Induced B-Cell Responses

“…In this analysis, a repertoire can be derived from a single subject or pooled from multiple subjects with identical or similar immune or antigen conditions. We applied this approach to a well-characterized eVLP-based vaccine candidate with proven efficacy in multiple animal models, including mice ( 50 , 52 ).…”

“…Ebola virus-like particles were produced as previously described ( 52 ). Briefly, 293T cells were co-transfected with EBOV (Kikwit) GP 1,2 and matrix protein, VP40.…”

Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus

“…12,13,51 This uses a replication-restricted, recombinant vesicular stomatitis virus (rVSV*DG) expressing luciferase, which is pseudotyped with either the VEEV IAB E1/E2 glycoproteins (Trinidad donkey) or Ebola GP (Kikwit 1995). 51 Briefly, heat-inactivated mouse sera (56 C for 30 min) was first diluted 1:20, followed by 5-fold serial dilutions that were mixed with an equal volume of Eagle's minimum essential medium with Earle's salts and 10% fetal bovine sera containing 4,000 fluorescent focus units of VEEV E1/E2 or EBOV GP pseudovirions and 10% guinea pig complement (Cedarlane, Burlington, NC). The sera and pseudovirion mixture was incubated overnight at 4 C. Following this incubation, 50 mL was inoculated onto Vero-76 cell monolayers in clear bottom, black-walled 96-well plates in duplicate.…”