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      Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice

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          Abstract

          Dengue virus (DENV) is the causative agent of dengue, and its incidence has increased 30-fold in the past five decades. Among the four cocirculating serotypes, DENV3 is associated with an increased number of severe infections and has become widespread. Vaccination is the mainstay of prevention in reducing disease burden. Previously, the protective efficacy of DNA vaccine candidates toward DENV1, 2, and 4 was confirmed in mice. In this study, a DNA vaccine candidate (pVAX1-D3ME) expressing the prM and E proteins of DENV3 was constructed, and then the immunogenicity and protection were assessed in mice to further develop a tetravalent dengue vaccine. Moreover, the cross-reactive immune responses against the other three serotypes were investigated. The results showed that three doses of 50 μg of pVAX1-D3ME were sufficient to induce strong antigen-specific T cell responses and robust and consistent neutralizing antibodies. Additionally, immunization with pVAX1-D3ME offered protective immunity against not only DENV3 but also the other three serotypes, which could be observed even after 12 months. This study shows great promise for the further evaluation of a dengue tetravalent DNA vaccine candidate in large animal models, including non-human primates.

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          Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity

          Dengue, a mosquito-borne virus of humans, infects over 50 million people annually. Infection with any of the four dengue serotypes induces protective immunity to that serotype, but does not confer long-term protection against infection by other serotypes. The immunological interactions between serotypes are of central importance in understanding epidemiological dynamics and anticipating the impact of dengue vaccines. We analysed a 38-year time series with 12 197 serotyped dengue infections from a hospital in Bangkok, Thailand. Using novel mechanistic models to represent different hypothesized immune interactions between serotypes, we found strong evidence that infection with dengue provides substantial short-term cross-protection against other serotypes (approx. 1–3 years). This is the first quantitative evidence that short-term cross-protection exists since human experimental infection studies performed in the 1950s. These findings will impact strategies for designing dengue vaccine studies, future multi-strain modelling efforts, and our understanding of evolutionary pressures in multi-strain disease systems.
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            Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents

            Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019.
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              The changing epidemiology of dengue in China, 1990-2014: a descriptive analysis of 25 years of nationwide surveillance data

              Background Dengue has been a notifiable disease in China since 1 September 1989. Cases have been reported each year during the past 25 years of dramatic socio-economic changes in China, and reached a historical high in 2014. This study describes the changing epidemiology of dengue in China during this period, to identify high-risk areas and seasons and to inform dengue prevention and control activities. Methods We describe the incidence and distribution of dengue in mainland China using notifiable surveillance data from 1990-2014, which includes classification of imported and indigenous cases from 2005-2014. Results From 1990-2014, 69,321 cases of dengue including 11 deaths were reported in mainland China, equating to 2.2 cases per one million residents. The highest number was recorded in 2014 (47,056 cases). The number of provinces affected has increased, from a median of three provinces per year (range: 1 to 5 provinces) during 1990-2000 to a median of 14.5 provinces per year (range: 5 to 26 provinces) during 2001-2014. During 2005-2014, imported cases were reported almost every month and 28 provinces (90.3%) were affected. However, 99.8% of indigenous cases occurred between July and November. The regions reporting indigenous cases have expanded from the coastal provinces of southern China and provinces adjacent to Southeast Asia to the central part of China. Dengue virus serotypes 1, 2, 3, and 4 were all detected from 2009-2014. Conclusions In China, the area affected by dengue has expanded since 2000 and the incidence has increased steadily since 2012, for both imported and indigenous dengue. Surveillance and control strategies should be adjusted to account for these changes, and further research should explore the drivers of these trends. Please see related article: http://dx.doi.org/10.1186/s12916-015-0345-0 Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0336-1) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                17 March 2020
                2020
                : 10
                : 87
                Affiliations
                [1] 1Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University , Beijing, China
                [2] 2Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University , Beijing, China
                [3] 3Yunnan Provincial Key Laboratory of Vector-borne Disease Control and Research, Yunnan Institute of Parasitic Diseases , Pu'er, China
                [4] 4Center of Epilepsy, Beijing Institute for Brain Disorders , Beijing, China
                Author notes

                Edited by: Gong Cheng, Tsinghua University, China

                Reviewed by: Jianfeng Dai, Soochow University, China; Yongfen Xu, Institut Pasteur of Shanghai (CAS), China

                *Correspondence: Hui Chen chenhuicxh@ 123456ccmu.edu.cn

                This article was submitted to Virus and Host, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2020.00087
                7089926
                32257963
                d7ac1c7e-9c28-4279-9005-f47aeeb5b996
                Copyright © 2020 Feng, Zheng, Wang, Gao, Fan, Sheng, Zhou, Chen and An.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 December 2019
                : 19 February 2020
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 53, Pages: 12, Words: 7989
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81372935
                Award ID: 81671971
                Award ID: 81772172
                Award ID: U1602223
                Funded by: Beijing Municipal Commission of Education 10.13039/501100002888
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                dengue virus,dna vaccine,prm-e,immunization,cross-protection
                Infectious disease & Microbiology
                dengue virus, dna vaccine, prm-e, immunization, cross-protection

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