Abstract
Human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) are major contributors to the global disease burden with many experts recognizing the requirement of an effective vaccine to bring a durable end to these viral epidemics. The most promising vaccine candidates that have advanced into pre-clinical models and the clinic to eliminate or provide protection against these chronic viruses are viral vectors [e.g., recombinant cytomegalovirus, Adenovirus, and modified vaccinia Ankara (MVA)]. This raises the question, is there a need to develop DNA vaccines against HIV-1 and HCV? Since the initial study from Wolff and colleagues which showed that DNA represents a vector that can be used to express transgenes durably in vivo, DNA has been regularly evaluated as a vaccine vector albeit with limited success in large animal models and humans. However, several recent studies in Phase I-IIb trials showed that vaccination of patients with recombinant DNA represents a feasible therapeutic intervention to even cure cervical cancer, highlighting the potential of using DNA for human vaccinations. In this review, we will discuss the limitations and the strategies of using DNA as a vector to develop prophylactic T cell-mediated vaccines against HIV-1 and HCV. In particular, we focus on potential strategies exploiting DNA vectors to elicit protective localized CD8+ T cell immunity in the liver for HCV and in the cervicovaginal mucosa for HIV-1 as localized immunity will be an important, if not critical component, of an efficacious vaccine against these viral infections.
Highlights
Human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) are significant contributors to the global disease burden with ∼36.9 million people living with HIV-1 and at least 71 million people persistently infected with HCV (WHO, 2017; UNAIDS, 2018)
HIV-1 and HCV coinfections represent an additional obstacle (Platt et al, 2016) a recent clinical study suggests that co-administration of HIV-1 and HCV vaccines in humans can elicit robust HIV1- and HCV-specific T cell responses without perturbing the immunodominance hierarchies of T cells responding against the vaccine encoded HIV-1 or HCV antigens (Hartnell et al, 2018)
DNA has recently re-emerged as an effective vaccination platform in humans, but its use in developing a T cell-based vaccine will likely rely on its ability to be exploited in a regimen that can elicit robust immunity in the vagina and the gut in the context of HIV-1, or the liver in the context of HCV
Summary
Human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) are significant contributors to the global disease burden with ∼36.9 million people living with HIV-1 and at least 71 million people persistently infected with HCV (WHO, 2017; UNAIDS, 2018). It is imperative that vaccines take into account the virus tropism, transmission routes, pathogenesis and immune responses that provide effective resistance against infections to elicit protective immunity against HIV-1 and/or HCV.
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