Oral vaccination of wildlife against rabies: Differences among host species in vaccine uptake efficiency

Abstract

Oral vaccination using attenuated and recombinant rabies vaccines has been proven a powerful tool to combat rabies in wildlife. However, clear differences have been observed in vaccine titers needed to induce a protective immune response against rabies after oral vaccination in different reservoir species. The mechanisms contributing to the observed resistance against oral rabies vaccination in some species are not completely understood. Hence, the immunogenicity of the vaccine virus strain, SPBN GASGAS, was investigated in a species considered to be susceptible to oral rabies vaccination (red fox) and a species refractory to this route of administration (striped skunk). Additionally, the dissemination of the vaccine virus in the oral cavity was analyzed for these two species. It was shown that the palatine tonsils play a critical role in vaccine virus uptake. Main differences could be observed in palatine tonsil infection between both species, revealing a locally restricted dissemination of infected cells in foxes. The absence of virus infected cells in palatine tonsils of skunks suggests a less efficient uptake of or infection by vaccine virus which may lead to a reduced response to oral vaccination. Understanding the mechanisms of oral resistance to rabies virus vaccine absorption and primary replication may lead to the development of novel strategies to enhance vaccine efficacy in problematic species like the striped skunk.

Responsiveness of various reservoir species to oral rabies vaccination correlates with differences in vaccine uptake of mucosa associated lymphoid tissues

“…1b and 2). These data confirmed previous snapshots of SPBN GASGAS vaccine virus infection of red fox peripheral tonsil layers 36 and demonstrate the utility of GFP-labelled vaccine virus strains for in-vivo tracking. Limitation of both vertical and lateral spread of virus infection, strongly indicate a spatio-temporal restriction of vaccine virus tropism and replication in tonsils of foxes.…”

“…The reasons for these obvious differences remain elusive. As discussed before 36 , the morphology of the lymphoreticular tissue of the pharynx cannot explain the observed differences in vaccine uptake among the species studied here. All species had a comparable anatomic configuration of Waldeyer's tonsillar ring with a dominating t. palatina.…”

“…Hence, presently all available oral rabies vaccines are live replication-competent virus constructs. Based on our previous findings 36 , this study aimed at elucidating the species-specific uptake, distribution and kinetics of oral rabies vaccines in the oral cavity of the most important terrestrial rabies reservoir www.nature.com/scientificreports www.nature.com/scientificreports/ species in order to identify barriers for immunisation with a focus on species known to be rather refractory to oral vaccination. To this end, in this first comparative and comprehensive in vivo tracking study with a standardised approach, we used a genetically modified vaccine virus construct, followed by up-to date techniques in imaging and viral RNA detection.…”

“…To this end, in this first comparative and comprehensive in vivo tracking study with a standardised approach, we used a genetically modified vaccine virus construct, followed by up-to date techniques in imaging and viral RNA detection. Earlier studies could identify infected cells 36,37 . In this study, using the SAD L16 GFP construct we were also able to identify cells in which active virus gene expression took place.…”

“…Previous studies demonstrated that the t. palatina is a main target tissue for infection by orally administered RABV vaccines [36][37][38] . In the pilot study, we focused on the red fox as the species, which is very responsive to oral rabies vaccination.…”