Bacterium-Like Particles Displaying the Rift Valley Fever Virus Gn Head Protein Induces Efficacious Immune Responses in Immunized Mice

Abstract

Rift Valley fever virus (RVFV), a mosquito-borne zoonotic phlebovirus, causes serious disease in humans and ruminants. According to the World Health Organization, Rift Valley fever is classified as a priority disease, and as such, vaccine development is of high priority due to the lack of licensed vaccines. In this study, a bacterium-like particle vaccine (BLP), RVFV-BLPs, is constructed. A novel display system is described, which is based on non-living and non-genetically modified Gram-positive bacterial cells, designated as Gram-positive enhancer matrix (GEM). The RVFV Gn head protein was displayed on the surface of GEM by co-expression with the peptidoglycan-binding domain (protein anchor) at the C-terminus. We determined that the RVFV Gn head-PA fusion protein was successfully displayed on the GEM. Mice immunized with RVFV-BLPs produced humoral and cellular immunity. Interestingly, comparing the production of RVFV Gn head-specific IgG and its subtype by vaccinating with different antigen doses of the RVFV-BLPs determined that the RVFV-BLPs (50 μg) group showed a greater effect than the other two groups. More importantly, antibodies produced by mice immunized with RVFV-BLPs (50 μg) exhibited potent neutralizing activity against RVFV pseudovirus. RVFV-BLPs (50 μg) also could induce IFN-γ and IL-4 in immunized mice; these mice generated memory cells among the proliferating T cell population after immunization with RVFV-BLPs with effector memory T cells as the major population, which means that RVFV-BLPs is an effective vaccine to establish a long-lived population of memory T cells. The findings suggest that the novel RVFV-BLPs subunit vaccine has the potential to be considered a safe and effective candidate vaccine against RVFV infection.

A Bivalent Bacterium-like Particles-Based Vaccine Induced Potent Immune Responses against the Sudan Virus and Ebola Virus in Mice

“…In this study, the ratios of IgG2a/IgG1 were analyzed. It was shown that S/ZBLP + 2 + P elicited balanced T1-and T2type immune responses in mice that were consistent with our previous results [34]. Te type I interferon includes IFNα and IFNβ and plays a vital role in early virus infection.…”

“…In our previous studies, BLPs vaccines for Middle East Respiratory Syndrome (MERS), Rift Valley fever (RVF), Sudan virus disease (SVD), and Zika were generated and induced both cellular and humoral immune responses in mice [29,[34][35][36]. Here, we prepare an EBOV-BLPs subunit vaccine that displays the ectodomain of EBOV GP on the surface of BLPs by PA.…”

Intranasally inoculated bacterium-like particles displaying porcine epidemic diarrhea virus S1 protein induced intestinal mucosal immune response in mice

“…The treated L. lactis (GEM) particles were centrifuged, and the pellet was washed three times with PBS. Finally, the GEM particles (GEMs) were re-suspended in PBS at a concentration of 2.5×10 9 particles/mL, which was referred to as 1 U ( 28 ). The GEM particles were directly used for the preparation of S1-BLPs or stored at -20°C.…”

Advances and perspectives in the development of vaccines against highly pathogenic bunyaviruses

“…Interestingly, while the results showed that IgG and nAbs were elicited after immunization, the immunogenicity was not dose-dependent. The induction of specific memory T-cells demonstrate the possibility for long-term protection ( Table 2 ) ( Zhang et al., 2022 ).…”