Impact of Molecular Modifications on the Immunogenicity and Efficacy of Recombinant Raccoon Poxvirus-Vectored Rabies Vaccine Candidates in Mice.

Carly M Malavé,Tonie E Rocke,Jorge E Osorio,Jaime Lopera-Madrid,Lex G Medina-Magües

doi:10.3390/vaccines9121436

Carly M Malavé, Tonie E Rocke + Show 3 more

Open Access

https://doi.org/10.3390/vaccines9121436

Copy DOI

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

Introduction

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]

Objectives

Methods

Results

Conclusion