Incorporation of membrane-anchored flagellin or Escherichia coli heat-labile enterotoxin B subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs

Frontiers in Microbiology
Yinglin QiXianzhu Xia

Abstract

Rabies remains an important worldwide public health threat, so safe, effective, and affordable vaccines are still being sought. Virus-like particle-based vaccines targeting various viral pathogens have been successfully produced, licensed, and commercialized. Here, we designed and constructed two chimeric rabies virus-like particles (cRVLPs) containing rabies virus (RABV) glycoprotein (G), matrix (M) protein, and membrane-anchored flagellin (EVLP-F) or Escherichia coli heat-labile enterotoxin B subunit (EVLP-L) as molecular adjuvants to enhance the immune response against rabies. The immunogenicity and potential of cRVLPs as novel rabies vaccine were evaluated by intramuscular vaccination in mouse and dog models. Mouse studies demonstrated that both EVLP-F and EVLP-L induced faster and larger virus-neutralizing antibodies (VNAs) responses and elicited greater numbers of CD4(+) and CD8(+) T cells secreting IFN-γ or IL-4 compared with a standard rabies VLP (sRVLP) containing only G and M. Moreover, cRVLPs recruited and/or activated more B cells and dendritic cells in inguinal lymph nodes. EVLP-F induced a strong, specific IgG2a response but not an IgG1 response, suggesting the activation of Th1 class immunity; in contrast, Th2 cl...Continue Reading

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Citations

Jun 16, 2017·Viral Immunology·Yulia BurakovaJishu Shi
Aug 29, 2019·Frontiers in Cellular and Infection Microbiology·Qiangde DuanGuoqiang Zhu
Aug 7, 2017·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Velasco Cimica, Jose M Galarza
Jun 29, 2021·Seminars in Cancer Biology·Xiao Yin MaFei Wen

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Methods Mentioned

BETA
transmission electron microscopy
enzyme-linked immunosorbent assay
flow cytometry
Electron microscopy
ELISA

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