Chimeric rabies virus-like particles containing membrane-anchored GM-CSF enhances the immune response against rabies virus.

Hongtao Kang,Yuwei Gao,Hualei Wang,Xianzhu Xia,Nan Li,Xuexing Zheng,Yinglin Qi,Songtao Yang

doi:10.3390/v7031134

Hongtao Kang, Yuwei Gao + Show 6 more

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https://doi.org/10.3390/v7031134

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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.

Highlights

Rabies is one of the oldest zoonotic diseases that occurs worldwide and afflicts most mammalian hosts
Our results demonstrate that immunization with chimeric rabies VLP (cRVLP) containing granulocyte-macrophage colony-stimulating factor (GM-CSF) is more efficient than standard rabies VLP (sRVLP) in inducing specific anti-rabies virus (RABV) immune responses in a mouse model
The results showed several gold particles located on the surface of EVLP-G when murine GM-CSF antibody was used as the primary antibody (Figure 1F)

Summary

Introduction

Rabies is one of the oldest zoonotic diseases that occurs worldwide and afflicts most mammalian hosts. The host manifests clinical symptoms of rabies, the result is almost invariably lethal [1]. Most human cases occur in the developing countries of Africa and Asia, where bites from rabid dogs are the major cause [3]. Vaccination is still the most effective way to prevent and control rabies in animals and humans. There has been a dramatic reduction in human rabies cases in most developed countries due to mass the vaccination of domestic animals [4]. The development of a more affordable, safe, and potent rabies vaccine is advisable and necessary

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