New insights into pathogenesis point to HIV-1 Tat as a key vaccine target.

Content Provider	Europe PMC
Author	Ensoli, Barbara Moretti, Sonia Borsetti, Alessandra Maggiorella, Maria Teresa Buttò, Stefano Picconi, Orietta Tripiciano, Antonella Sgadari, Cecilia Monini, Paolo Cafaro, Aurelio
Abstract	Despite over 30 years of enormous effort and progress in the field, no preventative and/or therapeutic vaccines against human immunodeficiency virus (HIV) are available. Here, we briefly summarize the vaccine strategies and vaccine candidates that in recent years advanced to efficacy trials with mostly unsatisfactory results. Next, we discuss a novel and somewhat contrarian approach based on biological and epidemiological evidence, which led us to choose the HIV protein Tat for the development of preventive and therapeutic HIV vaccines. Toward this goal, we review here the role of Tat in the virus life cycle as well as experimental and epidemiological evidence supporting its key role in the natural history of HIV infection and comorbidities. We then discuss the preclinical and clinical development of a Tat therapeutic vaccine, which, by improving the functionality and homeostasis of the immune system and by reducing the viral reservoir in virologically suppressed vaccinees, helps to establish key determinants for intensification of combination antiretroviral therapy (cART) and a functional cure. Future developments and potential applications of the Tat therapeutic vaccine are also discussed, as well as the rationale for its use in preventative strategies. We hope this contribution will lead to a reconsideration of the current paradigms for the development of HIV/AIDS vaccines, with a focus on targeting of viral proteins with key roles in HIV pathogenesis.
ISSN	03048608
Journal	Archives of Virology
Volume Number	166
PubMed Central reference number	PMC8363864
Issue Number	11
PubMed reference number	34390393
e-ISSN	14328798
DOI	10.1007/s00705-021-05158-z
Language	English
Publisher	Springer Vienna
Publisher Date	2021-08-14
Publisher Place	Vienna
Access Restriction	Open
Rights License	This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. © The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2021
Content Type	Text
Resource Type	Article
Subject	Virology Medicine