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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,*
College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China
Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China
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;
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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