Immunogenicity of a truncated enterovirus 71 VP1 protein fused to a Newcastle disease virus nucleocapsid protein fragment in mice

Ch’ng, Wei-Choong; Saw, W. T.; Yusoff, Khatijah; Shafee, Norazizah

doi:10.4149/av_2011_03_227

Cited by 7 publications

(9 citation statements)

References 24 publications

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“…As expected, the NPfl and NPt-VP1 1-100 proteins showed an approximate molecular weight of 55 and 60 kDa, respectively (Figure 1A). Band patterns obtained were similar to our previous reports [3,6,7]. The purified proteins were then used to vaccinate newborn hamsters as described above.…”

Section: Resultssupporting

confidence: 82%

“…To test the protective efficacy of the NPt-VP1 1-100 in this mouse model, we initially tested its immunogenicity in mice. It was found to be a potent immunogen in adult mice [6]. Based on these information, we performed an extensive viral challenge studies in the above newborn mouse model.…”

Section: Resultsmentioning

confidence: 99%

“…Initially, the full length NP (NPfl) and NPt-VP1 1-100 recombinant proteins were induced and purified as described previously [6,7]. The EV71 P5 was obtained from the Department of Pathology, Faculty of Medicine, Universiti Malaya, Malaysia [5].…”

Section: Resultsmentioning

confidence: 99%

“…Their survival rate was monitored until the end of the experiment on day 18 post-challenge when they were sacrificed via cardiac puncture to collect their sera for further analysis. All the collected sera were subjected to an indirect enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis against purified full length VP1 and NPfl proteins as described previously [6,7]. …”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters

Ch’ng

Stanbridge

Wong

et al. 2012

Virol J

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Enterovirus 71 (EV71) causes severe neurological diseases resulting in high mortality in young children worldwide. Development of an effective vaccine against EV71 infection is hampered by the lack of appropriate animal models for efficacy testing of candidate vaccines. Previously, we have successfully tested the immunogenicity and protectiveness of a candidate EV71 vaccine, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP11-100) protein, in a mouse model of EV71 infection. A drawback of this system is its limited window of EV71 susceptibility period, 2 weeks after birth, leading to restricted options in the evaluation of optimal dosing regimens. To address this issue, we have assessed the NPt-VP11-100 candidate vaccine in a hamster system, which offers a 4-week susceptibility period to EV71 infection. Results obtained showed that the NPt-VP11-100 candidate vaccine stimulated excellent humoral immune response in the hamsters. Despite the high level of antibody production, they failed to neutralize EV71 viruses or protect vaccinated hamsters in viral challenge studies. Nevertheless, these findings have contributed towards a better understanding of the NPt-VP11-100 recombinant protein as a candidate vaccine in an alternative animal model system.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters

Ch’ng

Stanbridge

Wong

et al. 2012

Virol J

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show abstract

“…The fact that passive transfer of specific antiserum provides protection against EV71 lethal challenge clearly illustrates not only the important role of humoral immunity in the control of EV71 but also the feasibility of vaccination [33]. Several EV71 vaccine candidates, including live-attenuated virus [30], inactivated whole virus [33,54,61-64], recombinant viral protein [65-67], virus-like particles and DNA vaccines [66,68,69], have been developed, and their immunogenicity and efficiency have been evaluated in animal models.…”

Section: Reviewmentioning

confidence: 99%

Animal models of enterovirus 71 infection: applications and limitations

Wang

2014

J Biomed Sci

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Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models.

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Partial protection against enterovirus 71 (EV71) infection in a mouse model immunized with recombinant newcastle disease virus capsids displaying the EV71 VP1 fragment

Ch’ng

Stanbridge

Ong

et al. 2011

Journal of Medical Virology

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Enterovirus 71 (EV71) infection may cause severe neurological complications, particularly in young children. Despite the risks, there are still no commercially available EV71 vaccines. Hence, a candidate vaccine construct, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP1(1-100) ) protein, was evaluated in a mouse model of EV71 infection. Previously, it was shown that this protein construct provoked a strong immune response in vaccinated adult rabbits. That study, however, did not address the issue of its effectiveness against EV71 infection in young animals. In the present study, EV71 viral challenge in vaccinated newborn mice resulted in more than 40% increase in survival rate. Significantly, half of the surviving mice fully recovered from their paralysis. Histological analysis of all of the surviving mice revealed a complete clearance of EV71 viral antigens from their brains and spinal cords. In hind limb muscles, the amounts of the antigens detected correlated with the degrees of tissue damage and paralysis. Findings from this study provide evidence that immunization with the NPt-VP1(1-100) immunogen in a newborn mouse model confers partial protection against EV71 infection, and also highlights the importance of NPt-VP1(1-100) as a possible candidate vaccine for protection against EV71 infections.

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Immunogenicity of a truncated enterovirus 71 VP1 protein fused to a Newcastle disease virus nucleocapsid protein fragment in mice

Cited by 7 publications

References 24 publications

Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters

Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters

Animal models of enterovirus 71 infection: applications and limitations

Partial protection against enterovirus 71 (EV71) infection in a mouse model immunized with recombinant newcastle disease virus capsids displaying the EV71 VP1 fragment

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