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

Abstract

Oral rabies vaccination (ORV) is highly effective in foxes and raccoon dogs, whereas for unknown reasons the efficacy of ORV in other reservoir species is less pronounced. To investigate possible variations in species-specific cell tropism and local replication of vaccine virus, different reservoir species including foxes, raccoon dogs, raccoons, mongooses, dogs and skunks were orally immunised with a highly attenuated, high-titred GFP-expressing rabies virus (RABV). Immunofluorescence and RT-qPCR screenings revealed clear differences among species suggesting host specific limitations to ORV. While for responsive species the palatine tonsils (tonsilla palatina) were identified as a main site of virus replication, less virus dissemination was observed in the tonsils of rather refractory species. While our comparison of vaccine virus tropism emphasizes the important role that the tonsilla palatina plays in eliciting an immune response to ORV, our data also indicate that other lymphoid tissues may have a more important role than originally anticipated. Overall, these data support a model in which the susceptibility to oral live RABV vaccine infection of lymphatic tissue is a major determinant in vaccination efficacy. The present results may help to direct future research for improving vaccine uptake and efficacy of oral rabies vaccines under field conditions.

Comparable Long-Term Rabies Immunity in Foxes after IntraMuscular and Oral Application Using a Third-Generation Oral Rabies Virus Vaccine

“…Follow-up studies will be performed to clarify this interesting point. Although we cannot exclude differences for IgG3 and IgG4 isotypes, our data exclude significant influences of the primary target cells for vaccine virus infection in the mucosa or lymphoid tonsil tissues [ 32 ] and muscle tissue. However, further efforts are required to fully understand antibody-related RABV protection, as there seem to be exceptions from the rule.…”

“…Next to the adaptive immune response, there is evidence that attenuated RABVs also activate the host innate immune responses [ 31 ]. Notably, virus gene expression in lymphoid tissue cells after oral vaccine uptake [ 32 ] and the ensuing cytokine induction, antigen processing, and presentation are crucial for the recruitment of antigen-presenting cells (APC), in particular dendritic cells (DCs), for initiation and shaping of adaptive T- and B-cell mediated immune responses [ 33 ]. Initiation of CD4+ and CD8+ T cell responses after RABV infection independent of the virus used has been described [ 34 ], with live RABV vector vaccines able to elicit both a type 1 and 2 immune response [ 35 ].…”

Ecological and Evolutionary Challenges for Wildlife Vaccination

“…Random binary immunization outcomes are often incorporated into SIR models by effectively lowering vaccination coverage by the proportion of binary failures [23]. However, if certain host types are more prone to vaccine failure, then it might be critical to address how these different failure rates among different host classes affect disease dynamics [24].…”

Neuroglia infection by rabies virus after anterograde virus spread in peripheral neurons

“…Apart from astrocytes, in vivo infection of non-neuronal muscle, epidermal, and epithelial cells have been described [ 5 , 12 , 13 , 43 ]. In foxes, which had been orally immunized with live-attenuated RABV, infected cells can be detected in the epithelium of lymphoid tonsils [ 57 , 64 ]. In vitro, even immature dendritic cells (DCs) or monocytes can be infected [ 36 ].…”