Toward DNA-Based T-Cell Mediated Vaccines to Target HIV-1 and Hepatitis C Virus: Approaches to Elicit Localized Immunity for Protection.

Authors:
Branka Grubor-Bauk
Branka Grubor-Bauk
University of Adelaide
Australia
Ashish C Shrestha
Ashish C Shrestha
Qld 2School of Medicine
Charani Ranasinghe
Charani Ranasinghe
The John Curtin School of Medical Research
Australia
Rowena A Bull
Rowena A Bull
School of Biotechnology and Biomolecular Sciences
Andrew R Lloyd
Andrew R Lloyd
University of New South Wales
Australia
Eric J Gowans
Eric J Gowans
Macfarlane Burnet Institute for Medical Research and Public Health
Australia

Front Cell Infect Microbiol 2019 3;9:91. Epub 2019 Apr 3.

Virology Laboratory, Basil Hetzel Institute for Translational Health Research, Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia.

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 , 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.

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Source
https://www.frontiersin.org/article/10.3389/fcimb.2019.00091
Publisher Site
http://dx.doi.org/10.3389/fcimb.2019.00091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456646PMC
April 2019
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