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Chimeric Rabies Virus-Like Particles Containing Membrane-Anchored GM-CSF Enhances the Immune Response against Rabies Virus

by Hongtao Kang 1,2,†, Yinglin Qi 2,3,†, Hualei Wang 2, Xuexing Zheng 2, Yuwei Gao 2, Nan Li 2, Songtao Yang 2,3,* and Xianzhu Xia 1,2,3,*
1
College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China
2
Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China
3
College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun 130062, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Curt Hagedorn
Viruses 2015, 7(3), 1134-1152; https://doi.org/10.3390/v7031134
Received: 27 December 2014 / Revised: 13 February 2015 / Accepted: 24 February 2015 / Published: 11 March 2015
(This article belongs to the Section Antivirals & Vaccines)
Rabies remains an important public health threat in most developing countries. To develop a more effective and safe vaccine against rabies, we have constructed a chimeric rabies virus-like particle (VLP), which containing glycoprotein (G) and matrix protein (M) of rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, and membrane-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF), and it was named of EVLP-G. The immunogenicity and protective efficacy of EVLP-G against RABV were evaluated by intramuscular administration in a mouse model. The EVLP-G was successfully produced in insect cells by coinfection with three recombinant baculoviruses expressing G, M, and GM-CSF, respectively. The membrane-anchored GM-CSF possesses a strong adjuvant activity. More B cells and dendritic cells (DCs) were recruited and/or activated in inguinal lymph nodes in mice immunized with EVLP-G. EVLP-G was found to induce a significantly increased RABV-specific virus-neutralizing antibody and elicit a larger and broader antibody subclass responses compared with the standard rabies VLP (sRVLP, consisting of G and M). The EVLP-G also elicited significantly more IFN-γ- or IL-4-secreting CD4+ and CD8+ T cells than the sRVLP. Moreover, the immune responses induced by EVLP-G protect all vaccinated mice from lethal challenge with RABV. These results suggest that EVLP-G has the potential to be developed as a novel vaccine candidate for the prevention and control of animal rabies. View Full-Text
Keywords: rabies virus; virus-like particles; GM-CSF; rabies vaccine rabies virus; virus-like particles; GM-CSF; rabies vaccine
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Kang, H.; Qi, Y.; Wang, H.; Zheng, X.; Gao, Y.; Li, N.; Yang, S.; Xia, X. Chimeric Rabies Virus-Like Particles Containing Membrane-Anchored GM-CSF Enhances the Immune Response against Rabies Virus. Viruses 2015, 7, 1134-1152.

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