Abstract
Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.
Highlights
Chronic infection with hepatitis C virus (HCV) is a serious global health problem
Peptide sequences derived from HCV antigens exhibit varying degrees of homology with different adenoviral (Ad) vector proteins
HCV antigens E1, E2, P7 and NS2 showed low homology (
Summary
Chronic infection with hepatitis C virus (HCV) is a serious global health problem. It affects ~170 million people worldwide and can lead to liver cirrhosis, hepatocellular carcinoma and end-stage liver diseases [1,2,3]. Current treatment of chronic HCV infection is limited to combination drug therapies, which are highly expensive, have serious side effects and have variable success rates in different viral genotypes and patient populations [4]. Development of vaccines to prevent and/or cure HCV infection is of paramount importance. Natural protection from infection is often used to model strategies to develop new vaccines. The immune mechanisms and correlates of viral clearance and protection from HCV infection have been studied extensively, but they still remain unclear [5,6,7].
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