期刊
VACCINES
卷 9, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/vaccines9030301
关键词
Rift Valley fever virus; bacterial superglue; multimeric protein scaffold particles; sheep; Gn head domain
资金
- Zoonotic Anticipation and Preparedness Initiative (ZAPI project
- IMI Grant Agreement) [115760]
- IMI
- European Commission
By combining self-assembling multimeric protein scaffold particles (MPSPs) and bacterial superglue, antigens can be bound to particles in their native conformation, improving the immunogenicity of a candidate subunit vaccine against the zoonotic Rift Valley fever virus (RVFV). Experimental results showed that the Gn head domain coupled to lumazine synthase-based MPSP reduced mortality in mice and protected lambs from viremia and clinical signs after immunization.
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 short-comings 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.
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