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

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.

doi:10.3389/fcimb.2019.00091

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

Journal Article · Wed Apr 03 00:00:00 EDT 2019 · Frontiers in Cellular and Infection Microbiology

DOI:https://doi.org/10.3389/fcimb.2019.00091· OSTI ID:1560575

Mekonnen, Zelalem A. ^[1]; Grubor-Bauk, Branka ^[1]; Masavuli, Makutiro G. ^[1]; Shrestha, Ashish C. ^[1]; Ranasinghe, Charani ^[2]; Bull, Rowena A. ^[3]; Lloyd, Andrew R. ^[3]; Gowans, Eric J. ^[1]; Wijesundara, Danushka K. ^[1]

Univ. of Adelaide, SA (Australia). Basil Hetzel Inst. for Translational Health Research, Virology Lab.
Australian National Univ., Canberra, ACT (Australia)
Univ. of New South Wales, Sydney, NSW (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 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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1560575

Journal Information:: Frontiers in Cellular and Infection Microbiology, Vol. 9, Issue APR; ISSN 2235-2988

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
DNA vaccine
hepatitis C
human immunodeficiency virus
HIV/AIDS
HCV
tissue-resident memory
T cell immunity

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