Abstract
Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm3g-1) have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD) as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 μg)/SV-140 (500 μg) and FD oE2 (100 μg)/SV-140 (500 μg) to induce long-term immunity was compared to immunisation with oE2 (100 μg) together with the conventional adjuvant Quil-A from the Quillaja saponira (10 μg) in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells) at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 μg SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications.
Highlights
Development of veterinary vaccine comes with a spectrum of challenges, as the storage, shipping and administration of the vaccine should be easy and the cost of veterinary vaccine production needs to be kept low. [1] Subunit vaccines often need to be refrigerated, require addition of adjuvants and need to be administered multiple times in order to induce long-term immunity
The samples freeze-dried with different concentrations of trehalose and glycine looked voluminous and snow-like (Fig 1A), as opposed to samples freeze-dried without excipients, which failed to form a freeze-dried cake (Fig 1B) The FD optimised E2 (oE2)/silica vesicles (SV)-140 developed with combination of 5% trehalose and 0.1% glycine as excipients reconstituted within 10 seconds on addition of 1 mL of water
The integrity of the vesicles following freeze-drying with 5% trehalose and 0.1% glycine was further confirmed by transmission electron microscope (TEM) and scanning electron microscope (SEM) analyses
Summary
Development of veterinary vaccine comes with a spectrum of challenges, as the storage, shipping and administration of the vaccine should be easy and the cost of veterinary vaccine production needs to be kept low. [1] Subunit vaccines often need to be refrigerated, require addition of adjuvants and need to be administered multiple times in order to induce long-term immunity. [1] Subunit vaccines often need to be refrigerated, require addition of adjuvants and need to be administered multiple times in order to induce long-term immunity. The storage stability of the subunit vaccines can be improved by freeze-drying the vaccine formulations Excipients such as sugars, surfactants, amino acids and polymers are typically added to the vaccine formulations to prevent degradation in the freeze-drying process and aide in the reconstitution of vaccines prior to use. [5] The major source of new BVDV-1 infection in herds come from the secretions or body fluids of persistently infected or acutely infected animals. [7] The current BVDV-1 vaccine approved for use in Australia needs to be refrigerated at 2°C to 8°C BVDV-1 infection of cattle has been highly investigated in several countries as it causes tremendous economic losses to the cattle industry. [5] The major source of new BVDV-1 infection in herds come from the secretions or body fluids of persistently infected or acutely infected animals. [6] Immunosuppression caused by BVDV-1 infection can lead to a secondary infection, which is a major cause of death in BVDV-1 infected cattle. [7] The current BVDV-1 vaccine approved for use in Australia needs to be refrigerated at 2°C to 8°C
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