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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / genetics
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Animals
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Antibodies, Neutralizing / blood
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Antibodies, Viral / blood
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Disease Models, Animal
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Female
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Glycoproteins / genetics
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Glycoproteins / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Injections, Intramuscular
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Interferon-gamma / metabolism
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Interleukin-4 / metabolism
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Mice, Inbred BALB C
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Rabies / prevention & control*
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Rabies Vaccines / administration & dosage
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Rabies Vaccines / genetics
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Rabies Vaccines / immunology*
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Rabies virus / genetics
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Rabies virus / immunology*
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
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Vaccines, Virus-Like Particle / administration & dosage
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Vaccines, Virus-Like Particle / genetics
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Vaccines, Virus-Like Particle / immunology*
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Neutralizing
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Antibodies, Viral
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Antigens, Viral
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Glycoproteins
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Rabies Vaccines
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Vaccines, Synthetic
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Vaccines, Virus-Like Particle
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Viral Envelope Proteins
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Viral Matrix Proteins
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glycoprotein G, Rabies virus
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Interleukin-4
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor