Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

Ming Zhou,Songqin Zhou,Zhen F Fu,Ling Zhao,Lijun Tang,Zhao Wang,Lei Wang,Ziming Jia,Min Cui,Juncheng Ruan

doi:10.18632/oncotarget.5904

Abstract

Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.

Highlights

Rabies is caused by the rabies virus (RABV) and is one of the oldest zoonoses in history
Recombinant RABV expressing murine granulocytemacrophage colony-stimulating factor (GM-CSF) has been constructed and shown to stimulate protective immunity after oral immunization in mice [38], dog GM-CSF was cloned into RABV as shown in Figure 1A to overcome the possible species specificity [43]
The recombinant RABV expressing dog GM-CSF is designated as LBNSE-dGM-CSF and was rescued using the procedures described previously [38]

Summary

Introduction

Rabies is caused by the rabies virus (RABV) and is one of the oldest zoonoses in history Today, it remains a public health threat causing more than 55,000 human deaths per year worldwide, most of which occurs in the developing countries of Asia and Africa [1]. It remains a public health threat causing more than 55,000 human deaths per year worldwide, most of which occurs in the developing countries of Asia and Africa [1] In these places, infected dog bites are the major reason for the high incidence of human rabies, control of canine rabies is the most cost-effective approach to eliminate human rabies [2, 3]. Developing an efficient rabies vaccine for free-roaming dogs is crucial for rabies control in these countries

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