HIV-1 Vaccine Trials: Evolving Concepts and Designs



Missa P Sanou 1, Anne S De Groot 2, Michael Murphey-Corb 3, Jay A Levy 4, Janet K Yamamoto*, 1
1 Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA
2 EpiVax Inc., University of Rhode Island, Providence, RI 02903, USA
3 Department of Infectious Diseases and Microbiology, University of Pittsburgh, E1252 Biomedical Science Tower 200, Lothrop Street, Pittsburgh, PA 15261, USA
4 Department of Medicine, University of California San Francisco, S-1280, 513 Parnassus Ave, San Francisco, CA 94143, USA


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© Sanou et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA; Tel: (352) 294-4145; Fax: (352) 392-7128; E-mail: yamamoto@ufl.edu


Abstract

An effective prophylactic HIV-1 vaccine is needed to eradicate the HIV/AIDS pandemic but designing such a vaccine is a challenge. Despite many advances in vaccine technology and approaches to generate both humoral and cellular immune responses, major phase-II and -III vaccine trials against HIV/AIDS have resulted in only moderate successes. The modest achievement of the phase-III RV144 prime-boost trial in Thailand re-emphasized the importance of generating robust humoral and cellular responses against HIV. While antibody-directed approaches are being pursued by some groups, others are attempting to develop vaccines targeting cell-mediated immunity, since evidence show CTLs to be important for the control of HIV replication. Phase-I and -IIa multi-epitope vaccine trials have already been conducted with vaccine immunogens consisting of known CTL epitopes conserved across HIV subtypes, but have so far fallen short of inducing robust and consistent anti-HIV CTL responses. The concepts leading to the development of T-cell epitope-based vaccines, the outcomes of related clinical vaccine trials and efforts to enhance the immunogenicity of cell-mediated approaches are summarized in this review. Moreover, we describe a novel approach based on the identification of SIV and FIV antigens which contain conserved HIV-specific T-cell epitopes and represent an alternative method for developing an effective HIV vaccine against global HIV isolates.

Keywords: Vaccine, clinical trials, HIV, SIV, FIV, multi-epitope, conserved epitopes..