Virus‐Like Particle‐Based Countermeasures Against Rift Valley Fever Virus

Abstract

Summary Rift Valley fever virus (RVFV) is an arbovirus that causes significant morbidity and mortality in both humans and livestock. With increased world travel and the threat of bioterrorism, there is a real risk of RVFV spreading to naïve geographical areas (Trans. R. Soc. Trop. Med. Hyg., 73, 1979, 618; MMWR Morb. Mortal. Wkly Rep., 49, 2000, 905). The introduction of RVFV would cause critical public health, agricultural and economic damage. Despite the clear need for an efficacious vaccine, there are no United States (US) Food and Drug Administration or US Department of Agriculture approved vaccines against RVFV. To address this need, a virus‐like particle (VLP)‐based vaccine candidate was developed. First, a non‐replicating chimeric RVF VLP vaccine candidate was generated that protected mice and rats against a lethal RVFV challenge. This was followed by the development and optimization of conditions for production of RVF VLPs in insect and mammalian cells. Immunological studies demonstrated that VLP‐based vaccine candidates elicit both humoral and cellular immune responses. Subsequent challenge studies using a lethal wild‐type RVFV strain under high‐containment conditions showed that RVF VLP vaccine candidates can completely protect mice and rats.

Enveloped virus‐like particles as vaccines against pathogenic arboviruses

“…These RFVF eVLPs were purified by ultracentrifugation and used for vaccination and protected mice from virus challenge [57]. Human HEK‐293 cells form yet another substrate for production of RVFV eVLPs and higher eVLP yields per cell could be obtained in this particular study compared to baculovirus‐infected Spodoptera frugiperda Sf21 insect cells [53, 58], however, the yield was not corrected for the much larger cell size of HEK‐293 in comparison to Sf21. Furthermore, scalability of DNA transfection of suspension HEK‐293 cells must be demonstrated first to assess feasibility of large‐scale eVLP production with this system.…”

Current Status of Rift Valley Fever Vaccine Development

“…A major advance in RVFV vaccine development is the assembly of structural RVFV proteins in eukaryotic expression systems to produce what is called virus-like particles (VLPs) [ 125 ]. VLPs mimic the overall structure of the virion without containing infectious genetic material.…”