Vaccine Efficacy of Self-Assembled Multimeric Protein Scaffold Particles Displaying the Glycoprotein Gn Head Domain of Rift Valley Fever Virus

Abstract

Compared to free antigens, antigens immobilized on scaffolds, such as nanoparticles, generally show improved immunogenicity. Conventionally, antigens are conjugated to scaffolds through genetic fusion or chemical conjugation, which may result in impaired assembly or heterogeneous binding and orientation of the antigens. By combining two emerging technologies—i.e., self-assembling multimeric protein scaffold particles (MPSPs) and bacterial superglue—these shortcomings can be overcome and antigens can be bound on particles in their native conformation. In the present work, we assessed whether this technology could improve the immunogenicity of a candidate subunit vaccine against the zoonotic Rift Valley fever virus (RVFV). For this, the head domain of glycoprotein Gn, a known target of neutralizing antibodies, was coupled on various MPSPs to further assess immunogenicity and efficacy in vivo. The results showed that the Gn head domain, when bound to the lumazine synthase-based MPSP, reduced mortality in a lethal mouse model and protected lambs, the most susceptible RVFV target animals, from viremia and clinical signs after immunization. Furthermore, the same subunit coupled to two other MPSPs (Geobacillus stearothermophilus E2 or a modified KDPG Aldolase) provided full protection in lambs as well.

Preliminary Evaluation of a Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Providing Full Protection against Heterologous Virulent Challenge in Cattle

“…At the time of design of the present study, we had preliminary mouse data that suggested Gn alone would be sufficient for protection (unpublished data); this is supported by the present cattle study. This finding is consistent with a RVFV Gn head domain vaccine study in sheep [ 41 ]. The other single dose group (group 3) in the present study was administered the GnGc vaccine 35 days prior to RVFV challenge and did not exhibit viremia and showed only transient RNAemia only for the RVFV L and M genes; however, one animal in this group had a slightly elevated body temperature for one day post challenge.…”

Intact Type I Interferon Receptor Signaling Prevents Hepatocellular Necrosis but Not Encephalitis in a Dose-Dependent Manner in Rift Valley Fever Virus Infected Mice

“…Previous studies showed that aerosol infection leads to more severe and earlier development of RVFE in mice than infection via intraperitoneal or subcutaneous injection [ 19 ]. Similarly, increased severity of RVF-associated disease after aerosol exposure has been reported in humans [ 19 , 20 , 21 , 22 , 23 ]. Large amounts of virus have been detected along the olfactory epithelium and the olfactory bulb in rats and mice that were intranasally infected [ 20 , 24 ].…”

Antimicrobial Potential of the Genera Geobacillus and Parageobacillus, as Well as Endolysins Biosynthesized by Their Bacteriophages

“…The E2 fusion and display system creates opportunities to develop novel applications in biotechnology and medicine, such as new vaccines [ 100 ]. The modified E2 scaffolds also have a potential to be used as nanocarriers in antimicrobial therapies, by fusion or encapsulation with recombinant molecules exhibiting antimicrobial properties.…”