The effect of enterovirus 71 immunization on neuropathogenesis and protein expression profiles in the thalamus of infected rhesus neonates

Chen, Huicheng; Zhang, Ying; Yang, Erxia; Liu, Longding; Che, Yanchun; Wang, Jingjing; Zhao, Hang; Tang, Donghong; Dong, Chuan; Yang, Li; Dong, Shen; Xi, Wang; Liao, Yun; Wang, Lichun; Na, Ruixiong; Liang, Yan; Li, Qihan

doi:10.1016/j.virol.2012.06.026

Cited by 14 publications

(13 citation statements)

References 42 publications

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“…The inactivated EV71 vaccine that we used in this experiment has been previously shown to induce an effective protective immune response, which was associated with gene modulation in animals [25], [31]. In this study, the EV71 vaccine was shown to induce highly variable gene expression profiles (Fig.…”

Section: Resultsmentioning

confidence: 78%

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

et al. 2013

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Enterovirus 71 (EV71), a major causative agent of hand-foot-and-mouth disease (HFMD), causes outbreaks among children in the Asia-Pacific region. A vaccine is urgently needed. Based on successful pre-clinical work, phase I and II clinical trials of an inactivated EV71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. In the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) of 30 infants (6 to 11 months) immunized with this vaccine or placebo and consented to join this study in the phase II clinical trial were analyzed. The results showed significantly greater neutralizing antibody and specific T cell responses in vaccine group after two inoculations on days 0 and 28. Additionally, more than 600 functional genes that were up- or down-regulated in PBMCs were identified by the microarray assay, and these genes included 68 genes associated with the immune response in vaccine group. These results emphasize the gene expression profile of the immune system in response to an inactivated EV71 vaccine in humans and confirmed that such an immune response was generated as the result of the positive mobilization of the immune system. Furthermore, the immune response was not accompanied by the development of a remarkable inflammatory response. Clinical Trial Registration: NCT01391494 and NCT01512706.

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Section: Resultsmentioning

confidence: 78%

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

et al. 2013

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“…Neonatal rhesus monkeys seem to be a relevant model for EV71-induced HFMD. Subsequent studies have shown that this neonatal monkey model was feasible for evaluating the efficacy of an inactivated EV71 vaccine [32]. …”

Section: Reviewmentioning

confidence: 99%

“…Non-human primates have also been used to test the immunogenicity and immunoprotection of potential EV71 vaccine candidates [32,61,68]. Macaque monkeys develop both specific humoral and cellular immune responses to both an inactivated EV71 vaccine and an EV71 virus-like particle (VLP) vaccine [68].…”

Section: Reviewmentioning

confidence: 99%

“…However, challenge experiments have not been performed to evaluate the efficacies of these vaccine candidates. Chen et al [32] reported that neonatal (1.5-month-old) rhesus monkeys that are intramuscularly immunized with a formalin-inactivated, alum-based EV71 vaccine exhibit repressed viral-induced inflammatory reactions in the CNS and reduced IL-6, IFN-γ, and TNF-α production. Adult rhesus monkeys that are immunized with the inactivated vaccine also exhibit good humoral and cellular immune responses and reduced pathologies and tissue viral loads upon live virus challenge [61].…”

Section: Reviewmentioning

confidence: 99%

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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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“…In Taiwan [24,25]. The predominant EV71 genotypes detected in Singapore were B3 in 1997-1999, B4 in 2000-2003, C1 in 2002, and B5 in 2006-2008. In mainland China, all strains were clustered in the C4 subgenotype of EV71 in 1998-2011 [26][27][28][29][30][31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Determinants of EV71 immunogenicity and protection against lethal challenge in a mouse model

Chang

Wei

et al. 2015

Immunol Res

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Circulating enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) is a major public health problem in the Asian-Pacific region. An EV71 vaccine for HFMD prevention is currently being developed. However, viral determinants that could influence the vaccine's efficacy have not been well characterized. In this study, we isolated and characterized several EV71 strains that are currently circulating in northern and southern China. We determined that VP1 variation is a major determinant of EV71 immunogenicity. A single amino acid variation in VP1 can lead to significant differences in the breadth and potency of immune responses against primary EV71 isolates as well as the sensitivity of EV71 to heterologous neutralizing antibody responses. We also identified EV71 strains that could induce potent immunogenic and cross-neutralizing antibody responses against diverse EV71 strains. Furthermore, these neutralizing antibodies could protect neonatal mice from lethal dose challenge with various circulating EV71 viruses. Our study provides useful information for EV71 vaccine development and evaluation.

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The effect of enterovirus 71 immunization on neuropathogenesis and protein expression profiles in the thalamus of infected rhesus neonates

Cited by 14 publications

References 42 publications

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

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

Animal models of enterovirus 71 infection: applications and limitations

Determinants of EV71 immunogenicity and protection against lethal challenge in a mouse model

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