Study of the Integrated Immune Response Induced by an Inactivated EV71 Vaccine

Liu, Longding; Zhang, Ying; Wang, Jingjing; Zhao, Hang; Jiang, Li; Che, Yanchun; Shi, Yanhong; Li, Rongcheng; Mo, Zhaojun; Huang, Teng; Liang, Zhenglun; Mao, Qunying; Wang, Lichun; Dong, Chuan; Liao, Yun; Guo, Lei; Yang, Erxia; Pu, Jing; Yue, Lei; Zhou, Zhenxin; Li, Qihan

doi:10.1371/journal.pone.0054451

Cited by 49 publications

(40 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…62 The extraction of total RNA from the PBMCs were performed using a RNA extraction kit (Qiagen, GmBH, Germany) according to the manufacturer's instructions. Total RNA was reverse transcribed into cDNA by PrimeScript TM RT reagent Kit with gDNA Eraser(Takara Bio, Japan).…”

Section: Real-time Rt-pcrmentioning

confidence: 99%

Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data

Zhang

Shao

et al. 2015

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

(2015) Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data, Human Vaccines & Immunotherapeutics, 11:3, 739-745, DOI: 10.1080/21645515.2015 The objective of this study was to find common immune mechanism across different kinds of vaccines. A metaanalysis of microarray datasets was performed using publicly available microarray Gene Expression Omnibus (GEO) and Array Express data sets of vaccination records. Seven studies (out of 35) were selected for this meta-analysis. A total of 447 chips (145 pre-vaccination and 302 post-vaccination) were included. Significance analysis of microarrays (SAM) program was used for screening differentially expressed genes (DEGs). Functional pathway enrichment for the DEGs was conducted in DAVID Gene Ontology (GO) database. Twenty DEGs were identified, of which 10 up-regulated genes involved immune response. Six of which were type I interferon (IFN) related genes, including LY6E, MX1, OAS3, IFI44L, IFI6 and IFITM3. Ten down-regulated genes mainly mediated negative regulation of cell proliferation and cell motion. Results of a subgroup analysis showed that although the kinds of genes varied widely between days 3 and 7 post vaccination, the pathways between them are basically the same, such as immune response and response to viruses, etc. For an independent verification of these 6 type I IFN related genes, peripheral blood mononuclear cells (PBMCs) were collected at baseline and day 3 after the vaccination from 8 Enterovirus 71(EV71) vaccinees and were assayed by RT-PCR. Results showed that the 6 DEGs were also upregulated in EV71 vaccinees. In summary, meta-analysis methods were used to explore the immune mechanism of vaccines and results indicated that the type I IFN related genes and corresponding pathways were common in early immune responses for different kinds of vaccines.

show abstract

Section: Real-time Rt-pcrmentioning

confidence: 99%

Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data

Zhang

Shao

et al. 2015

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…5,6 Three inactivated-EV71 vaccines had gone through Phase I-III clinical trials from December 2010 to March 2013 in China. [8][9][10][11][12][13][14][15] Those vaccines showed very good safety among children 6 m-5 y old. In addition, the vaccine efficacy in preventing EV71-associated HFMD was higher than 90%.…”

Section: Introductionmentioning

confidence: 99%

The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals

Mao

Wang

Shao

et al. 2015

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (7/9 and 8.9 ～228.1) than in the placebo group (1/10 and 0.8～1.7, P < 0.05). But no similar NTAb response trends were found in CA16 and 3 types of Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine coimmunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI.

show abstract

“…Various candidates against EV71 or CA16 virus, including inactivated vaccines (3,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), live attenuated vaccines (23,24), subunit vaccines based on the VP1 protein (25), virus-like particle (VLP) vaccines (26)(27)(28)(29)(30)(31)(32)(33)(34), and epitopebased vaccines (35)(36)(37)(38)(39), were shown to possess various levels of efficacy in animal studies or human clinical trials. In particular, inactivated EV71 vaccines showed promising results against EV71-associated diseases in recent phase 3 clinical studies conducted in mainland China (20)(21)(22).…”

mentioning

confidence: 99%

Cryo-Electron Microscopy Study of Insect Cell-Expressed Enterovirus 71 and Coxsackievirus A16 Virus-Like Particles Provides a Structural Basis for Vaccine Development

Gong

Zhu

Zhou

et al. 2014

J Virol

View full text Add to dashboard Cite

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common etiological agents responsible for the epidemics of hand, foot, and mouth disease (HFMD), a childhood illness with occasional severe neurological complications. A number of vaccine candidates against EV71 or CA16 have been reported; however, no vaccine is currently available for clinical use. Here, we generated a secreted version of EV71 and CA16 virus-like particles (VLPs) using a baculovirus-insect cell expression system and reconstructed the three-dimensional (3D) structures of both VLPs by cryo-electron microscopy (cryo-EM) single-particle analysis at 5.2-Å and 5.5-Å resolutions, respectively. The reconstruction results showed that the cryo-EM structures of EV71 and CA16 VLPs highly resemble the recently published crystal structures for EV71 natural empty particles and CA16 135S-like expanded particles, respectively. Our cryo-EM analysis also revealed that the majority of previously identified linear neutralizing epitopes are well preserved on the surface of EV71 and CA16 VLPs. In addition, both VLPs were able to induce efficiently neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71-and CA16-associated HFMD. IMPORTANCEThe recent outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region spurred the search for effective vaccines against EV71 and CA16 viruses, the two most common etiological agents responsible for HFMD. In this paper, we show that secreted versions of EV71 and CA16 VLPs generated in the baculovirus-insect cell expression system highly resemble the crystal structures of their viral conterparts and that the majority of previously identified linear neutralizing epitopes are well preserved on the VLP surfaces. In addition, the generated VLPs can efficiently induce neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71-and CA16-associated HFMD. Hand, foot, and mouth disease (HFMD) most frequently occurs in infants or children under 5 years old. Although most cases are mild and self-limited, HFMD can in some cases cause severe symptoms, such as myocarditis, pulmonary edema, and central nervous system complications ranging from flaccid paralysis to fatal encephalitis (1, 2). The recent epidemics of HFMD led to serious public health threats in the Asia Pacific region. In China, 1.16 million and 1.77 million cases of HFMD, including 353 and 905 deaths, were reported for 2009 and 2010, respectively (3). Etiologic studies revealed that enteroviruses, especially enterovirus 71 (EV71) and coxsackievirus A16 (CA16), are the most common causative agents responsible for HFMD epidemics (4-6). A clinical survey of the...

show abstract

Study of the Integrated Immune Response Induced by an Inactivated EV71 Vaccine

Cited by 49 publications

References 30 publications

Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data

Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data

The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals

Cryo-Electron Microscopy Study of Insect Cell-Expressed Enterovirus 71 and Coxsackievirus A16 Virus-Like Particles Provides a Structural Basis for Vaccine Development

Contact Info

Product

Resources

About