Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro . Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.

Crimean–Congo Hemorrhagic Fever Virus: Advances in Vaccine Development

“…Recombinant viruses have been extensively investigated as vectors in gene therapy and gene delivery for vaccine development. Viral expression systems explored for CCHF vaccine development comprise the modified Vaccinia Ankara virus ( MVA), 101,102 recombinant vesicular stomatitis virus (rVSV), 116 recombinant adenovirus type 5 (AdV-5), 90,103 and recombinant bovine herpesvirus type 4 (BoHV-4). 90 The MVA platform was used to deliver the GPC and the NP of the IbAr 10200 CCHFV strain.…”

“…Although the MVA-delivered NP induced humoral and cellular immune responses in vaccinated mice, the immune responses could not protect animals from lethal challenge infection. 102 A replicationcompetent recombinant VSV encoding the CCHFV GPC gene of the IbAr 10200 CCHFV strain yielded 100% protection in a STAT-1 À/À mouse model following single intraperitoneal immunization, while a replication-deficient VSV construct did not confer protection from intraperitoneally administered lethal virus challenge 116 (Table 1). The replication-competent construct developed nonsynonymous single nucleotide polymorphisms (SNPs), and two of these SNPs were nonsense mutations, which resulted in the truncation of part of the C-terminal tail of the Gc protein.…”

Crimean-Congo hemorrhagic fever virus strains Hoti and Afghanistan cause viremia and mild clinical disease in cynomolgus monkeys

“…Virus titration was performed by plaque assay using SW-13 cells (ATCC CCL-105) from all plasma and tissue samples as previously described [19]. Briefly, increasing 10-fold dilutions of the samples were adsorbed to SW-13 cell monolayers in duplicate wells (200 μl) and overlaid with 1.25% Avicel RC-581 (FMC BioPolymer, Philadelphia, PA) in 1x Eagles minimum essentials medium (MEM) with 5% FBS and 1% P/S).…”

“…Over the last decade several immunocompromised mouse models of CCHF have been developed [8,9]. While these models may have some utility for triaging antivirals and have been used to assess CCHFV vaccines [11,19,[41][42][43][44][45][46][47], they are not ideal, as these mice do not have intact immune PLOS NEGLECTED TROPICAL DISEASES systems and thus may not satisfy regulatory requirements for vaccine licensure under the US FDA Animal Rule [48].…”

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

“…The prime-boost group showed milder signs of infection and 100% of animals in both prime-only and prime-boost groups survived the challenge, while none of the mock-vaccinated did. 108…”