A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates

Chen, Hsin–Wei; Liu, Shih‐Jen; Li, Yi-Shiuan; Liu, Hsueh-Hung; Tsai, Jy‐Ping; Chiang, Chi‐Shiun; Chen, Meiyu; Hwang, Chyi-Sing; Huang, Chin‐Cheng; Hu, Huimei; Chung, Han-Hsuan; Wu, Sze-Hsien; Chong, Pele; Leng, Chih‐Hsiang; Pan, Chien-Hsiung

doi:10.1007/s00705-013-1639-1

Cited by 47 publications

(39 citation statements)

References 43 publications

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“…Alum was used as the adjuvant in this study, the immunization with EV71vac did not shift to a bias Th2 response (higher IL-4), but good IFN-γ responses instead. This IFN-γ skewing Th1 response is interesting and unlike other finding with subunit vaccines formulated with alum [29]. The difference may come from the remaining viral RNA in EV71vac that could function as a toll-like receptor agonist as proposed by Lin et al [28], or the immunogenic nature of EV71 capsid proteins as seen in EV71 infected adults [30].…”

Section: Discussionmentioning

confidence: 71%

Long-Term Immunogenicity Studies of Formalin-Inactivated Enterovirus 71 Whole-Virion Vaccine in Macaques

et al. 2014

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Enterovirus 71 (EV71) has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac) based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt) was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-γ and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.

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Section: Discussionmentioning

confidence: 71%

Long-Term Immunogenicity Studies of Formalin-Inactivated Enterovirus 71 Whole-Virion Vaccine in Macaques

et al. 2014

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“…There have been a few studies addressing CMI in NHP after DENV infection and vaccination (Table S1 in Supplementary Material). These studies have examined the induction of dengue-specific cytokine-producing cells from PBMC stimulated with purified DENV or NS1, NS3, or NS5 peptide pools, using ELISPOT or intracellular cytokine staining (ICS) or cytotoxicity assays (23, 25, 26, 28, 35, 39, 43, 45, 50–52). …”

Section: Current State Of the Nhp Model To Evaluate Dengue Vaccine Camentioning

confidence: 99%

Utility, Limitations, and Future of Non-Human Primates for Dengue Research and Vaccine Development

Sariol

White²

2014

Front. Immunol.

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Dengue is considered the most important emerging, human arboviruses, with worldwide distribution in the tropics. Unfortunately, there are no licensed dengue vaccines available or specific anti-viral drugs. The development of a dengue vaccine faces unique challenges. The four serotypes co-circulate in endemic areas, and pre-existing immunity to one serotype does not protect against infection with other serotypes, and actually may enhance severity of disease. One foremost constraint to test the efficacy of a dengue vaccine is the lack of an animal model that adequately recapitulates the clinical manifestations of a dengue infection in humans. In spite of this limitation, non-human primates (NHP) are considered the best available animal model to evaluate dengue vaccine candidates due to their genetic relatedness to humans and their ability to develop a viremia upon infection and a robust immune response similar to that in humans. Therefore, most dengue vaccines candidates are tested in primates before going into clinical trials. In this article, we present a comprehensive review of published studies on dengue vaccine evaluations using the NHP model, and discuss critical parameters affecting the usefulness of the model. In the light of recent clinical data, we assess the ability of the NHP model to predict immunological parameters of vaccine performances in humans and discuss parameters that should be further examined as potential correlates of protection. Finally, we propose some guidelines toward a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups.

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“…An alternative approach to the tetravalent vaccine based on all four DENV serotypes has recently been proposed [14][15][16]. Thus, a single subunit vaccine was generated incorporating a consensus DENV envelope protein domain III (cEDIII) and shown to induce the cross-neutralizing antibodies in mice.…”

Section: Introductionmentioning

confidence: 99%

Novel vaccination approach for dengue infection based on recombinant immune complex universal platform

Kim¹,

Reljić²,

Kilbourne³

et al. 2015

Vaccine

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A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates

Cited by 47 publications

References 43 publications

Long-Term Immunogenicity Studies of Formalin-Inactivated Enterovirus 71 Whole-Virion Vaccine in Macaques

Long-Term Immunogenicity Studies of Formalin-Inactivated Enterovirus 71 Whole-Virion Vaccine in Macaques

Utility, Limitations, and Future of Non-Human Primates for Dengue Research and Vaccine Development

Novel vaccination approach for dengue infection based on recombinant immune complex universal platform

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