quil-a and Bovine-Virus-Diarrhea-Mucosal-Disease

Topics: Adjuvants, Immunologic; Animals; Antibodies, Viral; Antibody Formation; Bovine Virus Diarrhea-Mucosal Disease; Cattle; CD8-Positive T-Lymphocytes; Diarrhea Virus 1, Bovine Viral; Dose-Response Relationship, Immunologic; Immunity, Cellular; Immunoglobulin G; Mice; Plant Extracts; Plant Leaves; Quillaja; Quillaja Saponins; Saponins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Th1-Th2 Balance; Viral Vaccines

Bovine Viral Diarrhoea Virus (BVDV) is widely distributed in cattle industries and causes significant economic losses worldwide annually. A limiting factor in the development of subunit vaccines for BVDV is the need to elicit both antibody and T-cell-mediated immunity as well as addressing the toxicity of adjuvants. In this study, we have prepared novel silica vesicles (SV) as the new generation antigen carriers and adjuvants. With small particle size of 50 nm, thin wall (~6 nm), large cavity (~40 nm) and large entrance size (5.9 nm for SV-100 and 16 nm for SV-140), the SV showed high loading capacity (∼ 250 μg/mg) and controlled release of codon-optimised E2 (oE2) protein, a major immunogenic determinant of BVDV. The in vivo functionality of the system was validated in mice immunisation trials comparing oE2 plus Quil A (50 μg of oE2 plus 10 μg of Quil A, a conventional adjuvant) to the oE2/SV-140 (50 μg of oE2 adsorbed to 250 μg of SV-140) or oE2/SV-140 together with 10 μg of Quil A. Compared to the oE2 plus Quil A, which generated BVDV specific antibody responses at a titre of 10(4), the oE2/SV-140 group induced a 10 times higher antibody response. In addition, the cell-mediated response, which is essential to recognise and eliminate the invading pathogens, was also found to be higher [1954-2628 spot forming units (SFU)/million cells] in mice immunised with oE2/SV-140 in comparison to oE2 plus Quil A (512-1369 SFU/million cells). Our study has demonstrated that SV can be used as the next-generation nanocarriers and adjuvants for enhanced veterinary vaccine delivery.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Bovine Virus Diarrhea-Mucosal Disease; Cattle; Diarrhea Virus 2, Bovine Viral; Drug Carriers; Female; Immunity, Cellular; Immunization; Mice; Mice, Inbred C57BL; Quillaja Saponins; Saponins; Silicon Dioxide; T-Lymphocytes; Viral Vaccines

Bovine viral diarrhea virus (BVDV) infections cause respiratory, reproductive, and enteric disease in cattle. Vaccination raises herd resistance and limits the spread of BVDV among cattle. Both killed and modified live vaccines against BVDV are available. While modified live vaccines elicit an immune response with a broader range and a longer duration of immunity, killed vaccines are considered to be safer. One way to improve the performance of killed vaccines is to develop new adjuvants. The goal of this research was evaluate new adjuvants, consisting of combinations of Quil A cholesterol and dimethyldioctadecylammonium (DDA) bromide, for use in killed vaccines. Responses to three novel killed vaccines, using combinations of Quil A and DDA as adjuvants, were compared to responses to a commercial modified live and a commercial killed vaccine. Vaccination response was monitored by measuring viral neutralizing antibodies (VN) levels and by response to challenge. All three novel vaccines were efficacious based on reduction in virus isolation, pyrexia, and depression. Compared to a commercial killed vaccine, the three novel vaccines elicited higher VN levels and reduced injection site inflammation.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Viral; Bovine Virus Diarrhea-Mucosal Disease; Cattle; Cholesterol; Diarrhea Viruses, Bovine Viral; Female; Male; Neutralization Tests; Quaternary Ammonium Compounds; Quillaja Saponins; Random Allocation; Saponins; Vaccination; Vaccines, Inactivated; Viral Vaccines