Characterization of the Biodistribution of a Silica Vesicle Nanovaccine Carrying a Rhipicephalus (Boophilus) microplus Protective Antigen With in vivo Live Animal Imaging

Karishma T Mody; Bing Zhang; Xun Li; Nicholas L Fletcher; Dewan T Akhter; Sandy Jarrett; Jun Zhang; Chengzhong Yu; Kristofer J Thurecht; Timothy J Mahony; Neena Mitter

doi:10.3389/fbioe.2020.606652

Characterization of the Biodistribution of a Silica Vesicle Nanovaccine Carrying a Rhipicephalus (Boophilus) microplus Protective Antigen With in vivo Live Animal Imaging

Front Bioeng Biotechnol. 2021 Jan 18:8:606652. doi: 10.3389/fbioe.2020.606652. eCollection 2020.

Authors

Affiliations

¹ Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, QLD, Australia.
² Animal Science, Queensland Department of Agriculture and Fisheries, St Lucia, QLD, Australia.
³ Centre for Advanced Imaging (CAI) and Australian Institute for Bioengineering and Nanotechnology (AIBN), ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St Lucia, QLD, Australia.
⁴ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.

Abstract

Development of veterinary subunit vaccines comes with a spectrum of challenges, such as the choice of adjuvant, antigen delivery vehicle, and optimization of dosing strategy. Over the years, our laboratory has largely focused on investigating silica vesicles (SVs) for developing effective veterinary vaccines for multiple targets. Rhipicephalus microplus (cattle tick) are known to have a high impact on cattle health and the livestock industry in the tropical and subtropical regions. Development of vaccine using Bm86 antigen against R. microplus has emerged as an attractive alternative to control ticks. In this study, we have investigated the biodistribution of SV in a live animal model, as well as further explored the SV ability for vaccine development. Rhodamine-labeled SV-140-C₁₈ (Rho-SV-140-C₁₈) vesicles were used to adsorb the Cy5-labeled R. microplus Bm86 antigen (Cy5-Bm86) to enable detection and characterization of the biodistribution of SV as well as antigen in vivo in a small animal model for up to 28 days using optical fluorescence imaging. We tracked the in vivo biodistribution of SVs and Bm86 antigen at different timepoints (days 3, 8, 13, and 28) in BALB/c mice. The biodistribution analysis by live imaging as well as by measuring the fluorescent intensity of harvested organs over the duration of the experiment (28 days) showed greater accumulation of SVs at the site of injection. The Bm86 antigen biodistribution was traced in lymph nodes, kidney, and liver, contributing to our understanding how this delivery platform successfully elicits antibody responses in the groups administered antigen in combination with SV. Selected tissues (skin, lymph nodes, spleen, kidney, liver, and lungs) were examined for any cellular abnormalities by histological analysis. No adverse effect or any other abnormalities were observed in the tissues.

Keywords: Bm86 antigen; adjuvants; biodistribution; immune response; in vivo imaging; live animal imaging; silica vesicles.