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Type: Journal article
Title: Toward DNA-based T-cell mediated vaccines to target HIV-1 and hepatitis C virus: approaches to elicit localized immunity for protection
Author: Grubor-Bauk, B.
Citation: Frontiers in Cellular and Infection Microbiology, 2019; 9(APR):91-1-91-8
Publisher: Frontiers Media
Issue Date: 2019
ISSN: 2235-2988
Statement of
Zelalem A. Mekonnen, Branka Grubor-Bauk, Makutiro G. Masavuli, Ashish C. Shrestha, Charani Ranasinghe, Rowena A. Bull, Andrew R. Lloyd, Eric J. Gowans, and Danushka K. Wijesundara
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.
Keywords: DNA vaccine; hepatitis C; human immunodeficiency virus; HIV/AIDS; HCV, tissue-resident memory; T cell immunity
Rights: © 2019 Mekonnen, Grubor-Bauk, Masavuli, Shrestha, Ranasinghe, Bull, Lloyd, Gowans and Wijesundara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
RMID: 0030113202
DOI: 10.3389/fcimb.2019.00091
Grant ID:
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