Vaccination with virus-like particles protects mice from lethal infection of Rift Valley Fever Virus

Abstract

Rift Valley Fever virus (RVFV) regularly accounts for severe and often lethal outbreaks among livestock and humans in Africa. Safe and effective veterinarian and human vaccines are highly needed. We present evidence that administration of RVF virus-like particles (VLPs) induces protective immunity in mice. In an accompanying paper, (Habjan, M., Penski, N., Wagner, V., Spiegel, M., Overby, A.K., Kochs, G., Huiskonen, J., Weber, F., 2009. Efficient production of Rift Valley fever virus-like particles: the antiviral protein MxA can inhibit primary transcription of Bunyaviruses. Virology 385, 400-408) we report the production of these VLPs in mammalian cells. After three subsequent immunizations with 1x10(6) VLPs/dose, high titers of virus-neutralizing antibodies were detected; 11 out of 12 mice were protected from challenge and only 1 out of 12 mice survived infection in the control groups. VLP vaccination efficiently suppressed replication of the challenge virus, whereas in the control animals high RNA levels and increasing antibody titers against the nucleocapsid protein indicated extensive viral replication. Our study demonstrates that the RVF VLPs are highly immunogenic and confer protection against RVFV infection in mice. In the test groups, the vaccinated mice did not exhibit any side effects, and the lack of anti-nucleocapsid protein antibodies serologically distinguished vaccinated animals from experimentally infected animals.

Creation of a Nonspreading Rift Valley Fever Virus

“…We and others have previously reported efficient VLP production systems and VLPs comprising only the Gn and Gc proteins are highly effective vaccine candidates (20,29,31,32,35,38). Mandell et al demonstrated that including the N protein in VLPs improves vaccine efficacy (31), which could be due to stabilization of the particle and/or to partial protective efficacy mediated by the N protein alone (11).…”

Recombinant Rift Valley fever vaccines induce protective levels of antibody in baboons and resistance to lethal challenge in mice

“…To address this concern, we developed and tested two rVACV vaccines for RVF for use in animals. Other vaccines in development for RVF include attenuated RVFV strains with deletions in the NSs gene (25), DNA, and subunit (27)(28)(29)(30). Recombinant poxvirus vaccines have been previously developed using the lumpy skin disease virus or the WR strain of VACV as vectors (31,32).…”

“…Inactivated RVFV vaccines, such as TGI-GSD-200, are safe for use in pregnant and young animals but are less immunogenic (27). Similarly, subunit and DNA vaccines are also safe but poorly immunogenic, requiring multiple immunizations (27)(28)(29). Another significant advantage of the rVACVs is their heat stability, thus eliminating the need for Initial vaccination was administered by scarification on day 0, and the intramuscular booster inoculation was given on day 28.…”

Single-Dose Immunization with Virus Replicon Particles Confers Rapid Robust Protection against Rift Valley Fever Virus Challenge

“…Examples of recently developed candidate vaccines include DNA-vectored (2,24,27), virus-like particle (VLP) (11,29,31), replicon particle (RRP) (23), and live attenuated (5, 13) vaccines. VLP candidates show promise and remarkable safety but generally require adjuvant and/or multiple immunizations for complete protection.…”