Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine

Abstract

Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN-luc, negative control) in mice and big brown bats (Eptesicus fuscus). Mice vaccinated and boosted intradermally with 1 x 107 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x107 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x108 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN-luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the efficacy of a novel, in silico designed rabies MoG antigen that conferred protection from rabies challenge in mice and big brown bats in laboratory studies. With further development, topical or oronasal administration of the RCN-MoG vaccine could potentially mitigate rabies in wild bat populations, reducing spillover of this deadly disease into humans, domestic mammals, and other wildlife.

Recombinant Human Adenovirus Type 5 Co-expressing RABV G and SFTSV Gn Induces Protective Immunity Against Rabies Virus and Severe Fever With Thrombocytopenia Syndrome Virus in Mice

“…As the major protective antigen of RABV, G protein is usually selected for novel rabies vaccine designation (Astray et al, 2017). At present, the recombinant vaccines based on poxvirus, adenovirus and parainfluenza expressing G protein of RABV have been studied, some of which have been successfully used for rabies prevention (Yarosh et al, 1996;Chen et al, 2013;Stading et al, 2017). Compared with traditional vaccines, these recombinant virus vaccines showed the advantages of better safety and immunogenicity.…”

Oncolytic properties of non-vaccinia poxviruses

“…The RCNV strain used in this study was originally isolated from apparently healthy raccoons [ 30 ] and has been shown to be avirulent in numerous animal models. Recombinant RCNV vaccines have been successfully employed in mice, raccoons, skunks, foxes, bobcats, rabbits, domestic cats, piglets, sheep, bats and non-human primates [ 55 , 57 – 62 ]. RCNV-vectored rabies vaccine has also been administered via oral, intranasal and conjunctival routes as a mucosal vaccine in cats and was found to be safe [ 60 ].…”

Defining New Pathways to Manage the Ongoing Emergence of Bat Rabies in Latin America

“…Moreover, naturally acquired VNAs from sublethal exposures potentially creates substantial baseline immunity not observed for carnivore reservoirs, which may also help reach effective herd immunity faster [55]. Existing recombinant viral vaccines using vaccinia [56,57] and raccoonpox [58,59] vectors are immunogenic and protective in bats. As both vectors are already used in large-scale campaigns targeting wildlife, they have been extensively tested for safety and lack of reversion to virulence in non-target species [48,60].…”