Oncotarget

Research Papers: Immunology:

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

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

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Oncotarget. 2015; 6:38504-38516. https://doi.org/10.18632/oncotarget.5904

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Abstract

Ming Zhou1,*, Lei Wang1,*, Songqin Zhou1,*, Zhao Wang1, Juncheng Ruan1, Lijun Tang3, Ziming Jia3, Min Cui1, Ling Zhao1 and Zhen F. Fu1,2

1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China

2 Department of Pathology, University of Georgia, Athens, GA, USA

3 Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Academy of Preventive Medicine, Wuhan, China

* These authors have contributed equally to this paper

Correspondence to:

Ling Zhao, email:

Zhen F. Fu, email:

Keywords: rabies, recombinant rabies virus, GM-CSF, oral vaccine, dog, Immunology and Microbiology Section, Immune response, Immunity

Received: July 12, 2015 Accepted: August 26, 2015 Published: September 30, 2015

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.


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