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      Heterologous Immunity between Adenoviruses and Hepatitis C Virus (HCV): Recombinant Adenovirus Vaccine Vectors Containing Antigens from Unrelated Pathogens Induce Cross-Reactive Immunity Against HCV Antigens

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          Abstract

          Host immune responses play an important role in the outcome of infection with hepatitis C virus (HCV). They can lead to viral clearance and a positive outcome, or progression and severity of chronic disease. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions implicating a role for unknown factors and events. In our earlier studies, we made a surprising discovery that peptides derived from structural and non-structural proteins of HCV have substantial amino acid sequence homologies with various proteins of adenoviruses and that immunizing mice with a non-replicating, non-recombinant adenovirus vector leads to induction of a robust cross-reactive cellular and humoral response against various HCV antigens. In this work, we further demonstrate antibody cross-reactivity between Ad and HCV in vivo. We also extend this observation to show that recombinant adenoviruses containing antigens from unrelated pathogens also possess the ability to induce cross-reactive immune responses against HCV antigens along with the induction of transgene antigen-specific immunity. This cross-reactive immunity can (a) accommodate the making of dual-pathogen vaccines, (b) play an important role in the natural course of HCV infection and (c) provide a plausible answer to many unexplained questions regarding immunity to HCV.

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          Most cited references55

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          Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence.

          In efforts to inform public health decision makers, the Global Burden of Diseases, Injuries, and Risk Factors 2010 (GBD2010) Study aims to estimate the burden of disease using available parameters. This study was conducted to collect and analyze available prevalence data to be used for estimating the hepatitis C virus (HCV) burden of disease. In this systematic review, antibody to HCV (anti-HCV) seroprevalence data from 232 articles were pooled to estimate age-specific seroprevalence curves in 1990 and 2005, and to produce age-standardized prevalence estimates for each of 21 GBD regions using a model-based meta-analysis. This review finds that globally the prevalence and number of people with anti-HCV has increased from 2.3% (95% uncertainty interval [UI]: 2.1%-2.5%) to 2.8% (95% UI: 2.6%-3.1%) and >122 million to >185 million between 1990 and 2005. Central and East Asia and North Africa/Middle East are estimated to have high prevalence (>3.5%); South and Southeast Asia, sub-Saharan Africa, Andean, Central, and Southern Latin America, Caribbean, Oceania, Australasia, and Central, Eastern, and Western Europe have moderate prevalence (1.5%-3.5%); whereas Asia Pacific, Tropical Latin America, and North America have low prevalence (<1.5%). The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival for those who already have evidence of liver disease. Copyright © 2012 American Association for the Study of Liver Diseases.
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            Adaptive immune responses in acute and chronic hepatitis C virus infection.

            The hepatitis C virus (HCV) persists in the majority of infected individuals and is a significant cause of human illness and death globally. Recent studies have yielded important insights into immunity to HCV, in particular revealing the central role of T cells in viral control and clearance. Other key features of adaptive immune responses remain obscure, including mechanisms by which T cells control HCV replication, the role of antibodies in conferring protection and how cellular and humoral immunity are subverted in persistent infection.
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              No one is naive: the significance of heterologous T-cell immunity.

              Memory T cells that are specific for one virus can become activated during infection with an unrelated heterologous virus, and might have roles in protective immunity and immunopathology. The course of each infection is influenced by the T-cell memory pool that has been laid down by a host's history of previous infections, and with each successive infection, T-cell memory to previously encountered agents is modified. Here, we discuss evidence from studies in mice and humans that shows the importance of this phenomenon in determining the outcome of infection.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                26 May 2019
                May 2019
                : 8
                : 5
                : 507
                Affiliations
                [1 ]Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2S2, Canada; Shakti1@ 123456ualberta.ca (S.S.); wl6@ 123456ualberta.ca (W.L.); Jiel@ 123456ualberta.ca (J.L.)
                [2 ]Department of Laboratory Medicine & Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2S2, Canada; Gupta1@ 123456ualberta.ca (N.G.); vedi@ 123456ualberta.ca (S.V.); saurabh@ 123456ualberta.ca (S.G.); rakesh.rkumar1988@ 123456gmail.com (R.K.)
                Author notes
                [* ]Correspondence: bagrawal@ 123456ualberta.ca ; Tel.: +1-780-492-0929
                Author information
                https://orcid.org/0000-0002-1957-6371
                https://orcid.org/0000-0001-6521-0998
                Article
                cells-08-00507
                10.3390/cells8050507
                6562520
                31130710
                e5f3a14d-8d0c-48b5-a55b-3cba4960ee45
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 April 2019
                : 24 May 2019
                Categories
                Article

                hepatitis c virus,heterologous immunity,adenoviruses,host response

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