Abstract
Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order Chiroptera) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is being used to manage rabies in other wildlife reservoirs like fox and raccoon, but no rabies vaccine is available for bats. We previously developed a recombinant raccoonpox virus (RCN) vaccine candidate expressing a mosaic glycoprotein (MoG) gene that protected mice and big brown bats when challenged with RABV. In this study, we developed two new recombinant RCN candidates expressing MoG (RCN-tPA-MoG and RCN-SS-TD-MoG) with the aim of improving RCN-MoG. We assessed and compared in vitro expression, in vivo immunogenicity, and protective efficacy in vaccinated mice challenged intracerebrally with RABV. All three candidates induced significant humoral immune responses, and inoculation with RCN-tPA-MoG or RCN-MoG significantly increased survival after RABV challenge. These results demonstrate the importance of considering molecular elements in the design of vaccines, and that vaccination with either RCN-tPA-MoG or RCN-MoG confers adequate protection from rabies infection, and either may be a sufficient vaccine candidate for bats in future work.
Highlights
Rabies is a devastating neurological disease that afflicts humans, domestic animals, and wildlife, and is caused by rabies virus (RABV), a negative strand lyssavirus of the family Rhabdoviridae
Immunofluorescence assays confirmed the presence of RABV glycoprotein antigen in raccoonpox virus (RCN)-tissue plasminogen activator (tPA)-mosaic glycoprotein (MoG), RCN-SS-transmembrane domain (TD)-MoG, and RCN-MoG when compared to RCN-GFP and the cell negative control (Figure 2)
RCN-tPA-MoG produced the highest mean of fluorescent particles, followed by RCN-SSTD-MoG, RCN-MoG (Table 1)
Summary
Rabies is a devastating neurological disease that afflicts humans, domestic animals, and wildlife, and is caused by rabies virus (RABV), a negative strand lyssavirus of the family Rhabdoviridae. In Central and South America, vampire bat rabies is responsible for the deaths of thousands of livestock and hundreds of human rabies cases annually [4,5,6]. The viral vector, vaccinia, causes disease in humans and cattle, raising questions about its safety profile for use in wild populations and vampire bats, in particular, due to their blood feeding habits [12,13]. Bats carry several antigenic variants of RABV and other phylogroup 1 (PG-1) lyssaviruses that cause rabies-like disease, precipitating the need for a vaccine with broader antigenic coverage [14,15,16]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.