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      Chimpanzee adenoviral vector prime-boost regimen elicits potent immune responses against Ebola virus in mice and rhesus macaques


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          In the last few decades, Ebola virus (EBOV) has emerged periodically and infected people in Africa, resulting in an extremely high mortality rate. With no available prophylaxis or cure so far, a highly effective Ebola vaccine is urgently needed. In this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, AdC7 and AdC68, which express glycoproteins (GP) of the EBOV strain identified in the 2014 outbreak. Our results indicated that a single immunization using AdC7 or AdC68 could stimulate potent EBOV-specific antibody responses, whereas the AdC7 prime-AdC68 boost regimen induced much stronger and sustained humoral and cellular immune responses in both mice and rhesus monkeys, compared with AdC7 or AdC68 single vaccination or the AdC68 prime-AdC7 boost regimen. This prime-boost vaccine could also protect mice from the simulated infection with EBOV-like particle (EBOVLP) in biosafety level 2 (BSL-2) laboratories, and antibodies from the prime-boost immunized rhesus macaques could passively provide protection against EBOVLP infection. Altogether, our results show that the AdC7 prime-AdC68 boost vaccine is a promising candidate for further development to combat EBOV infections.

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          Most cited references33

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          Adenoviruses as vaccine vectors

          Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles. They are attractive vaccine vectors as they induce both innate and adaptive immune responses in mammalian hosts. Currently, adenovirus vectors are being tested as subunit vaccine systems for numerous infectious agents ranging from malaria to HIV-1. Additionally, they are being explored as vaccines against a multitude of tumor-associated antigens. In this review we describe the molecular biology of adenoviruses as well as ways the adenovirus vectors can be manipulated to enhance their efficacy as vaccine carriers. We describe methods of evaluating immune responses to transgene products expressed by adenoviral vectors and discuss data on adenoviral vaccines to a selected number of pathogens. Last, we comment on the limitations of using human adenoviral vectors and provide alternatives to circumvent these problems. This field is growing at an exciting and rapid pace, thus we have limited our scope to the use of adenoviral vectors as vaccines against viral pathogens.
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            Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Preliminary Report.

            Background Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD), but little information is available about its prevalence or the duration of its persistence. We report the initial findings of a pilot study involving survivors of EVD in Sierra Leone. Methods We enrolled a convenience sample of 100 male survivors of EVD in Sierra Leone, at different times after their recovery from EVD, and recorded self-reported information about sociodemographic characteristics, the EVD episode, and health status. Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target-gene sequences of NP and VP40. Results A total of 93 participants provided an initial semen specimen for analysis, of whom 46 (49%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 9 men who had a specimen obtained 2 to 3 months after the onset of EVD, in the semen of 26 of 40 (65%) who had a specimen obtained 4 to 6 months after onset, and in the semen of 11 of 43 (26%) who had a specimen obtained 7 to 9 months after onset; the results for 1 participant who had a specimen obtained at 10 months were indeterminate. The median cycle-threshold values (for which higher values indicate lower RNA levels) were 32.0 with the NP gene target and 31.1 with the VP40 gene target for specimens obtained at 2 to 3 months, 34.5 and 32.3, respectively, for specimens obtained at 4 to 6 months, and 37.0 and 35.6, respectively, for specimens obtained at 7 to 9 months. Conclusions These data showed the persistence of Ebola virus RNA in semen and declining persistence with increasing months since the onset of EVD. We do not yet have data on the extent to which positivity on RT-PCR is associated with virus infectivity. Although cases of suspected sexual transmission of Ebola have been reported, they are rare; hence the risk of sexual transmission of the Ebola virus is being investigated. (Funded by the World Health Organization and others.).
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              Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells.

              The regulation of the subclass of immunoglobulin secreted by B cells has been studied in vitro in polyclonal systems using mitogens, such as lipopolysaccharide (LPS), to bypass the requirement for cognate interaction between antigen-specific T and B cells. In these systems, interleukin-(IL)-4 induces the secretion of IgG1 (ref. 1) and IgE (ref. 2); IL-5 enhances the secretion of IgA, and interferon-gamma (IFN-gamma) enhances the secretion of IgG2a (ref. 5). Clones of murine TH cells can be divided into two subsets, TH1 and TH2 (ref. 6). Both subsets synthesize IL-3 and granulocyte-monocyte colony-stimulating factor (GM-CSF), but only TH1 clones produce IL-2, IFN-gamma, and lymphotoxin (LT) and TH2 clones produce IL-4 and IL-5 (ref. 7). We have examined the role of clones of antigen-specific TH1 and TH2 cells in the regulation of the subclasses of IgG antibody secreted by antigen-specific B cells. Our results show that both types of TH cells induce the secretion of IgM and IgG3, whereas clones of TH1 and TH2 cells specifically induce antigen-specific B cells to secrete IgG2a and IgG1, respectively. We also demonstrate that regulation of commitment to the secretion of a particular IgG isotype occurs in two distinct stages: cognate interaction between T and B cells and interaction between T-cell-derived lymphokines and B cells.

                Author and article information

                Emerg Microbes Infect
                Emerg Microbes Infect
                Emerging Microbes & Infections
                Taylor & Francis
                24 July 2019
                : 8
                : 1
                : 1086-1097
                [a ]University of Chinese Academy of Sciences , Beijing, People’s Republic of China
                [b ]Vaccine Research Center, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences , Shanghai, People’s Republic of China
                [c ]Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai, People’s Republic of China
                [d ]Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, People’s Republic of China
                Author notes
                [CONTACT ] Dongming Zhou dmzhou@ 123456ips.ac.cn University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China; Vaccine Research Center, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, People’s Republic of China; Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin 300070, People’s Republic of China

                Supplemental data for this article can be accessed http://doi.org/10.1080/22221751.2019.1644968.

                © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 09 March 2019
                : 16 June 2019
                : 11 July 2019
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 50, Pages: 12
                Funded by: Xin-Lian-Xin BioMed Inc
                Funded by: Strategic Priority Research Program of the Chinese Academy of Sciences
                Award ID: XDB29040000
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 31870922
                Funded by: National Science and Technology Major Project
                Award ID: 2016YFC1201000,2018ZX10101004
                This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences: [Grant Number XDB29040000]; National Natural Science Foundation of China: [Grant Number 31870922]; National Science and Technology Major Project: [Grant Number 2016YFC1201000,2018ZX10101004], and Xin-Lian-Xin BioMed Inc., Wuxi, China. ( http://sinosbio.com).

                chimpanzee adenoviral vector,adc7,adc68,prime-boost,ebola vaccine


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