title: Chimeric rabies virus-like particles containing membrane-anchored GM-CSF enhances the immune response against rabies virus.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China. kang1989462@sina.com.|Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. kang1989462@sina.com.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Kang
authors.affiliation: Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. qiyinglin1985@163.com.|College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun 130062, China. qiyinglin1985@163.com.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. wangh25@hotmail.com.
authors.forename: Hualei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. zhengxx2513@gmail.com.
authors.forename: Xuexing
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. gaoyuwei@gmail.com.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. linan226@126.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. yst62041@163.com.|College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun 130062, China. yst62041@163.com.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China. xiaxzh@cae.cn.|Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China. xiaxzh@cae.cn.|College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun 130062, China. xiaxzh@cae.cn.
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000235:genetics; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D006023:Glycoproteins; D011819:Rabies Vaccines; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C064951:glycoprotein G, Rabies virus; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor