Enterovirus 71 vaccine: close but still far

Zhang, Dingmei; Lu, Jing; Lu, Jiahai

doi:10.1016/j.ijid.2009.12.002

Cited by 58 publications

(47 citation statements)

References 52 publications

(52 reference statements)

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“…The vaccine studies in animal models have demonstrated that neutralizing antibodies may play a critical role in protecting mice from the viral challenge [12,13,16]. EV71 vaccine clinical trials have been approved recently and will be soon carried out in China.…”

Section: Introductionmentioning

confidence: 99%

Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

Yang

Deng

Wan

et al. 2011

Virol J

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Enterovirus 71 (EV71) has emerged as a significant pathogen causing large outbreaks in China for the past 3 years. Developing an EV71 vaccine is urgently needed to stop the spread of the disease; however, the adaptive immune response of humans to EV71 infection remains unclear. We examined the neutralizing antibody titers in HFMD patients and compared them to those of asymptomatic healthy children and young adults. We found that 80% of HFMD patients became positive for neutralizing antibodies against EV71 (GMT = 24.3) one day after the onset of illness. The antibody titers in the patients peaked two days (GMT = 79.5) after the illness appeared and were comparable to the level of adults (GMT = 45.2). Noticeably, the antibody response was not correlated with disease severity, suggesting that cellular immune response, besides neutralizing antibodies, could play critical role in controlling the outcome of EV71 infection in humans.

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Section: Introductionmentioning

confidence: 99%

Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

Yang

Deng

Wan

et al. 2011

Virol J

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“…7 At present, there are no effective antiviral medications 8 and no prophylactic vaccine against EV71 infection. 9 EV71 was shown to be responsible in China for most of the fatalities associated with severe neurological manifestations ranging from aseptic meningitis to acute flaccid paralysis and brainstem encephalitis in children < 5 years of age. 6,10 Chang et al 11 reported that an extensive analysis of clinical observations showed that humoral immunity did not differ significantly among cases of different clinical severity, and most of the severe EV71 cases had a lower cellular T helper type 1 cytokine level plus a weaker lymphocyte proliferation response.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

“…Blood samples were obtained on days 1-7 after onset, discharge from the hospital (day [7][8][9][10][11][12][13][14] and the fully recovered stage (defined as 1 month after illness onset), respectively. All samples were collected specifically for this study and were coded to protect confidentiality.…”

Section: Recruitment and Sample Collectionmentioning

confidence: 99%

Dominant CD4‐dependent RNA‐dependent RNA polymerase‐specific T‐cell responses in children acutely infected with human enterovirus 71 and healthy adult controls

Dang

Gao

et al. 2014

Immunology

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SummaryHuman enterovirus 71 (EV71) is one of the major causes of hand, foot and mouth disease (HFMD), which leads to significant mortality in infected children. A prophylactic vaccine is urgently needed. However, little is known about the protective T-cell immunity in individuals infected with the EV71 virus. In this study, we performed a comprehensive ex vivo interferon-c ELISPOT analysis in 31 children infected with EV71 as well as in 40 healthy adult controls of the CD4 + and CD8 + T-cell responses to overlapping peptides spanning the VP1 structural protein and RNAdependent RNA polymerase (RdRp) non-structural protein. EV71-specific CD4 T-cell responses were detected in most of the acute patients and were mostly CD4-dependent RdRp-specific responses. CD8-dependent VP1 and RdRp-specific responses were also detected in a small proportion of recently infected children. There was no significant association between the strength of the T-cell responses and disease severity observed during the acute EV71 infection phase. Interestingly, an RdRp-specific, but no VP1-specific, CD4-dependent T-cell response was detected in 30% of the adult controls, and no T-cell responses were detected in healthy children. In addition, 24 individual peptides containing potential T-cell epitope regions were identified. The data suggest that CD4-dependent RdRp-specific T-cell responses may play an important role in protective immunity, and the epitopes identified in this study should provide valuable information for future therapeutic and prophylactic vaccine design as well as basic research.

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“…To date, there are no effective antiviral drugs to treat the EV71 infection nor is there commercially available vaccines to prevent the infection (Chen et al 2006;Ong et al 2010;Solomon et al 2010;Zhang and Lu 2010). Scientists have attempted to develop injectable vaccines against EV71, which include inactivatedwhole-virus vaccines (Ong et al 2010), DNA vaccines (Tung et al 2007), subunit/epitope peptide vaccines (Foo et al 2007;Wu et al 2001), and virus-like particle (VLP) vaccine (Chung et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Expression of enterovirus 71 virus-like particles in transgenic enoki (Flammulina velutipes)

Lin

Liu

Stark

et al. 2015

Appl Microbiol Biotechnol

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No commercial vaccines are currently available for enterovirus 71 (EV71) infection. Oral virus-like particle (VLP) vaccines are regarded as a better choice for prevention from food-borne diseases compared with injected whole virus vaccines. Unfortunately, the application of oral VLP vaccines produced from transgenic plants was limited due to the concerns of gene contamination. Alternatively, using transgenic mushrooms retains the advantages of transgenic plants and tremendously reduce risks of gene contamination. Polycistronic expression vectors harboring the glyceraldehyde-3-phospho-dehydrogenase promoter to codrive EV71 structural protein P1 and protease 3C using the 2A peptide of porcine teschovirus-1 were constructed and introduced into Flammulina velutipes via Agrobacterium tumefaciens-mediated transformation. The analyses of the genomic PCR, Southern blotting, and RT-PCR showed that the genes of P1 and 3C were integrated into the chromosomal DNA through a single insertion, and their resulting mRNAs were transcribed. The Western blotting analysis combined with LC-MS/MS demonstrated that EV71 VLPs were composed of the four subunit proteins digested from P1 polyprotein by 3C protease. Through the use of a single particle electron microscope, images of 1705 particles with diameter similar to the EV71 viron were used for 3D reconstruction. Protrusions were observed on the surface in the 2D class averages, and a 3D reconstruction of the VLPs was obtained. In conclusion, EV71 VLPs were successfully produced in transgenic F. velutipes using a polycistronic expression strategy, which indicates that this approach is promising for the development of oral vaccines produced in mushrooms.

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Enterovirus 71 vaccine: close but still far

Cited by 58 publications

References 52 publications

Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

Dominant CD4‐dependent RNA‐dependent RNA polymerase‐specific T‐cell responses in children acutely infected with human enterovirus 71 and healthy adult controls

Expression of enterovirus 71 virus-like particles in transgenic enoki (Flammulina velutipes)

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