Immunogenicity and protective efficacy of an EV71 virus-like particle vaccine against lethal challenge in newborn mice

Sun, Shiqi; Gao, Fan; Mao, Qunying; Shao, Jiang; Jiang, Liping; Liu, Dawei; Wang, Yiping; Yao, Xin; Wu, Xing; Sun, Bo; Zhao, Dandan; Ma, Yuanyuan; Lu, Jin‐Jian; Kong, Wei; Jiang, Chunlai; Liang, Zhenglun

doi:10.1080/21645515.2015.1053675

Cited by 12 publications

(12 citation statements)

References 42 publications

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“…Determination of the sedimentation coefficient of EV71 VLPs using analytical ultracentrifugation (AUC) indicated that they were smaller than the secreted EV71 VLPs purified by discontinuous cesium chloride density gradients but were similar to the empty capsids of natural EV71 virions reported previously [23, 24]. Altogether, this and previous studies not only show that the obtained EV71 VLPs were immunogenic and could induce neutralizing antibodies by immunization in mice [22], but they also provide a structural basis for the generation of VLP vaccines produced from Sf9 cells and purified by a novel multistep chromatography process. Such findings facilitate the potential development of an EV71 VLPs vaccine candidate against HFMD.…”

Section: Introductionsupporting

confidence: 73%

Characterization of human enterovirus71 virus-like particles used for vaccine antigens

Zhao

Sun

et al. 2017

PLoS ONE

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Human enterovirus 71 (EV71) is a major causative pathogen of hand, foot and mouth disease (HFMD) and has caused outbreaks with significant mortality among young children in the Asia-Pacific region in recent years. Towards developing a vaccine for this disease, we have expressed and purified EV71 virus-like particles (VLPs), which resemble the authentic virus in appearance, capsid structure and protein sequence, from insect cells (Sf9) using a multistep chromatography process. We demonstrated intracellular localization of the VLPs in host cells by in situ immunogold detection, electron microscopy and immunofluorescence. Characteristics of these EV71 VLPs were studied using a variety of immunological and physicochemical techniques, which aimed to reveal that the purified EV71 VLPs have good morphology and structure consistent with natural EV71 empty capsids. Results of the amino acid analysis, SDS-PAGE, Western blotting and high-performance liquid chromatography confirmed the high purity of the EV71 VLPs. However the sedimentation coefficient of the VLPs showed that they were smaller than that of secreted EV71 VLPs purified by discontinuous cesium chloride density gradients, they were similar to the empty capsids of natural EV71 virions reported previously. Combined with the previous study that EV71 VLPs purified by a multistep chromatography process were able to elicit strong humoral immune responses in mice, our results further supported the conclusion that our EV71 VLPs had well-preserved molecular and structural characteristics. The EV71 VLPs produced from the baculovirus expression system and purified by a multistep chromatography process displayed key structural and immunological features, which would contribute to their efficacy as a HFMD vaccine.

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Section: Introductionsupporting

confidence: 73%

Characterization of human enterovirus71 virus-like particles used for vaccine antigens

Zhao

Sun

et al. 2017

PLoS ONE

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“…Virus-like particles (VLPs) for EV-A71 are similar in morphology to the natural viral capsid structure and have been developed as potential vaccines 46 . Vaccination with an EV-A71 VLP vaccine showed significant potency against lethal challenge in newborn mice.…”

Section: Introductionmentioning

confidence: 99%

Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development

Chang

Chen

2018

Rev. Inst. Med. trop. S. Paulo

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Enterovirus A71 (EV-A71) infections are one of the main etiological agents of hand, foot and mouth disease (HFMD) and herpangina worldwide. EV-A71 infection is a life-threatening communicable disease and there is an urgent global need for the development of vaccines for its prevention and control. The morbidity rate of EV-A71 infection differs between countries. The pathogen’s genetic lineages are undergoing rapid evolutionary changes. An association between the occurrence of EV-A71 infection and the circulation of different genetic strains of EV-A71 virus has been identified around the world. In this review, we present and discuss the molecular epidemiology and pathogenesis of the human disease caused by EV-A71 infection, as well as current prospects for the development of an EV-A71 vaccine.

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“…Notwithstanding advancements in DNA vaccines [34], those containing recombinant protein subunits [35,36], and those containing live attenuated viruses [37][38][39], VLPs have yielded more advantageous recombinant vaccines. VLP vaccines can fuse multiple antigenic sites together to completely expose epitopes on the surface, thereby inducing a more effective immune response [20,22,[24][25][26][27]40]. A novel EV71 VLP lacking VP4 (designated VLP ΔVP4 ) structurally mimics the 80S empty capsid, which is the end stage of EV71 uncoating, thereby exhibiting desirable immunogenicity and protection as a vaccine candidate [22].…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant EV71 VLPs can resemble the natural virus structure in terms of their capsid proteins. Immunization with such VLPs can induce EV71-specific immune response with high neutralizing antibody titers and increased cytokines in mouse model [18,[25][26][27]. Considering the EV71 inactivated whole-virus vaccines are unable to prevent infection caused by other major agents of HFMD, such as CA16, CA10 and CA6, multivalent vaccines deriving from VLPs are regarded as another option for disease prevention [12,24].…”

Section: Introductionmentioning

confidence: 99%

Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections

Liu¹,

Zhao²,

Xue

et al. 2020

Virol J

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Background: Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection. Methods: To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured. Results: The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization. Conclusions: The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections.

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Immunogenicity and protective efficacy of an EV71 virus-like particle vaccine against lethal challenge in newborn mice

Cited by 12 publications

References 42 publications

Characterization of human enterovirus71 virus-like particles used for vaccine antigens

Characterization of human enterovirus71 virus-like particles used for vaccine antigens

Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development

Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections

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