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

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 strategiesmore » 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.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [3];  [3];  [1];  [1]
  1. Univ. of Adelaide, SA (Australia). Basil Hetzel Inst. for Translational Health Research, Virology Lab.
  2. Australian National Univ., Canberra, ACT (Australia)
  3. Univ. of New South Wales, Sydney, NSW (Australia)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1560575
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Frontiers in Cellular and Infection Microbiology
Additional Journal Information:
Journal Volume: 9; Journal Issue: APR; Journal ID: ISSN 2235-2988
Publisher:
Frontiers Research Foundation
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DNA vaccine; hepatitis C; human immunodeficiency virus; HIV/AIDS; HCV; tissue-resident memory; T cell immunity

Citation Formats

Mekonnen, Zelalem A., Grubor-Bauk, Branka, Masavuli, Makutiro G., Shrestha, Ashish C., Ranasinghe, Charani, Bull, Rowena A., Lloyd, Andrew R., Gowans, Eric J., and Wijesundara, Danushka K. Toward DNA-Based T-Cell Mediated Vaccines to Target HIV-1 and Hepatitis C Virus: Approaches to Elicit Localized Immunity for Protection. United States: N. p., 2019. Web. doi:10.3389/fcimb.2019.00091.
Mekonnen, Zelalem A., Grubor-Bauk, Branka, Masavuli, Makutiro G., Shrestha, Ashish C., Ranasinghe, Charani, Bull, Rowena A., Lloyd, Andrew R., Gowans, Eric J., & Wijesundara, Danushka K. Toward DNA-Based T-Cell Mediated Vaccines to Target HIV-1 and Hepatitis C Virus: Approaches to Elicit Localized Immunity for Protection. United States. doi:10.3389/fcimb.2019.00091.
Mekonnen, Zelalem A., Grubor-Bauk, Branka, Masavuli, Makutiro G., Shrestha, Ashish C., Ranasinghe, Charani, Bull, Rowena A., Lloyd, Andrew R., Gowans, Eric J., and Wijesundara, Danushka K. Wed . "Toward DNA-Based T-Cell Mediated Vaccines to Target HIV-1 and Hepatitis C Virus: Approaches to Elicit Localized Immunity for Protection". United States. doi:10.3389/fcimb.2019.00091. https://www.osti.gov/servlets/purl/1560575.
@article{osti_1560575,
title = {Toward DNA-Based T-Cell Mediated Vaccines to Target HIV-1 and Hepatitis C Virus: Approaches to Elicit Localized Immunity for Protection},
author = {Mekonnen, Zelalem A. and Grubor-Bauk, Branka and Masavuli, Makutiro G. and Shrestha, Ashish C. and Ranasinghe, Charani and Bull, Rowena A. and Lloyd, Andrew R. and Gowans, Eric J. and Wijesundara, Danushka K.},
abstractNote = {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.},
doi = {10.3389/fcimb.2019.00091},
journal = {Frontiers in Cellular and Infection Microbiology},
number = APR,
volume = 9,
place = {United States},
year = {2019},
month = {4}
}

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