Chimeric VLPs Based on HIV-1 Gag and a Fusion Rabies Glycoprotein Induce Specific Antibodies against Rabies and Foot-and-Mouth Disease Virus

Abstract

Foot and mouth disease is a livestock acute disease, causing economic losses in affected areas. Currently, control of this disease is performed by mandatory vaccination campaigns using inactivated viral vaccines. In this work, we describe the development of a chimeric VLP-based vaccine candidate for foot-and-mouth disease virus (FMDV), based on the co-expression of the HIV-1 Gag protein and a novel fusion rabies glycoprotein (RVG), which carries in its N-term the FMDV main antigen: the G-H loop. It is demonstrated by confocal microscopy that both Gag-GFP polyprotein and the G-H loop colocalize at the cell membrane and, that the Gag polyprotein of the HIV virus acts as a scaffold for enveloped VLPs that during the budding process acquires the proteins that are being expressed in the cell membrane. The obtained VLPs were spherical particles of 130 ± 40 nm in diameter (analyzed by TEM, Cryo-TEM and NTA) carrying an envelope membrane that efficiently display the GH-RVG on its surface (analyzed by gold immunolabeling). Immunostainings with a FMDV hyperimmune serum showed that the heterologous antigenic site, genetically fused to RVG, is recognized by specific G-H loop antibodies. Additionally, the cVLPs produced expose the G-H loop to the liquid surrounding (analyzed by specific ELISA). Finally, we confirmed that these FMD cVLPs are able to induce a specific humoral immune response, based on antibodies directed to the G-H loop in experimental animals.

Virus-like Particles: Fundamentals and Biomedical Applications

“…In another study, murine polyomavirus cVLPs were manipulated to elicit CD8 + and CD4 + T cells and antibody responses [ 70 ]. The immune response against other cVLPs has also been evaluated recently, specifically for the foot-and-mouth disease virus cVLP vaccine, based on the co-expression of the HIV-1 Gag protein and rabies glycoproteins [ 71 ].…”

Calibration and standardization of extracellular vesicle measurements by flow cytometry for translational prostate cancer research

“…Previous studies have reported a diameter for Gag-GFP-positive EVs of ∼115 nm as measured by NTA and electron microscopy. 28,33 Discrepancy in size measurement can be explained by variability in instrument sensitivity but also in EV isolation methodology used. In our study, only dual centrifugation at 2500g was used to remove platelets, cellular debris, and aggregates.…”

Nanovaccines against Animal Pathogens: The Latest Findings

“…Chimeric VLP-based nanovaccines against rabies and FMDV co-expressing a novel fusion rabies glycoprotein have been recently investigated. The authors also optimised VLP production in cell cultures by adding additives and demonstrated the production of specific Abs against both zoonotic diseases in mice, serving as a proof-of-concept recombinant FMDV vaccine candidate which would be easier to produce and safer than currently available vaccines [ 153 ]. The promise of VLPs is highly remarkable against fish pathogenic viruses in which delivery methods are inefficient.…”