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      HIV/AIDS vaccines for Africa: scientific opportunities, challenges and strategies

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          Abstract

          More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa.

          Most cited references94

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          HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells.

          Michael Betts, Martha Nason, Sadie West … (2006)
          Establishing a CD8(+) T cell-mediated immune correlate of protection in HIV disease is crucial to the development of vaccines designed to generate cell-mediated immunity. Historically, neither the quantity nor breadth of the HIV-specific CD8(+) T-cell response has correlated conclusively with protection. Here, we assess the quality of the HIV-specific CD8(+) T-cell response by measuring 5 CD8(+) T-cell functions (degranulation, IFN-gamma, MIP-1beta, TNF-alpha, and IL-2) simultaneously in chronically HIV-infected individuals and elite nonprogressors. We find that the functional profile of HIV-specific CD8(+) T cells in progressors is limited compared to that of nonprogressors, who consistently maintain highly functional CD8(+) T cells. This limited functionality is independent of HLA type and T-cell memory phenotype, is HIV-specific rather than generalized, and is not effectively restored by therapeutic intervention. Whereas the total HIV-specific CD8(+) T-cell frequency did not correlate with viral load, the frequency and proportion of the HIV-specific T-cell response with highest functionality inversely correlated with viral load in the progressors. Thus, rather than quantity or phenotype, the quality of the CD8(+) T-cell functional response serves as an immune correlate of HIV disease progression and a potential qualifying factor for evaluation of HIV vaccine efficacy.
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            Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia.

            Eric S. Rosenberg, James M. Billingsley, Angela Caliendo … (1997)
            Virus-specific CD4+ T helper lymphocytes are critical to the maintenance of effective immunity in a number of chronic viral infections, but are characteristically undetectable in chronic human immunodeficiency virus-type 1 (HIV-1) infection. In individuals who control viremia in the absence of antiviral therapy, polyclonal, persistent, and vigorous HIV-1-specific CD4+ T cell proliferative responses were present, resulting in the elaboration of interferon-gamma and antiviral beta chemokines. In persons with chronic infection, HIV-1-specific proliferative responses to p24 were inversely related to viral load. Strong HIV-1-specific proliferative responses were also detected following treatment of acutely infected persons with potent antiviral therapy. The HIV-1-specific helper cells are likely to be important in immunotherapeutic interventions and vaccine development.
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              Noncytolytic control of viral infections by the innate and adaptive immune response.

              L Guidotti, F V Chisari (2001)
              This review describes the contribution of noncytolytic mechanisms to the control of viral infections with a particular emphasis on the role of cytokines in these processes. It has long been known that most cell types in the body respond to an incoming viral infection by rapidly secreting antiviral cytokines such as interferon alpha/beta (IFN-alpha/beta). After binding to specific receptors on the surface of infected cells, IFN-alpha/beta has the potential to trigger the activation of multiple noncytolytic intracellular antiviral pathways that can target many steps in the viral life cycle, thereby limiting the amplification and spread of the virus and attenuating the infection. Clearance of established viral infections, however, requires additional functions of the immune response. The accepted dogma is that complete clearance of intracellular viruses by the immune response depends on the destruction of infected cells by the effector cells of the innate and adaptive immune system [natural killer (NK) cells and cytotoxic T cells (CTLs)]. This notion, however, has been recently challenged by experimental evidence showing that much of the antiviral potential of these cells reflects their ability to produce antiviral cytokines such as IFN-gamma and tumor necrosis factor (TNF)-alpha at the site of the infection. Indeed, these cytokines can purge viruses from infected cells noncytopathically as long as the cell is able to activate antiviral mechanisms and the virus is sensitive to them. Importantly, the same cytokines also control viral infections indirectly, by modulating the induction, amplification, recruitment, and effector functions of the immune response and by upregulating antigen processing and display of viral epitopes at the surface of infected cells. In keeping with these concepts, it is not surprising that a number of viruses encode proteins that have the potential to inhibit the antiviral activity of cytokines.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pan Afr Med J
                Journal ID (iso-abbrev): Pan Afr Med J
                Journal ID (publisher-id): PAMJ
                Title: The Pan African Medical Journal
                Publisher: The African Field Epidemiology Network
                ISSN (Electronic): 1937-8688
                Publication date (Electronic): 20 April 2015
                Publication date Collection: 2015
                Volume: 20
                Electronic Location Identifier: 386
                Affiliations
                [1 ]Department of Medical Microbiology, College of Health Sciences, University of Zimbabwe, P O Box A178, Avondale, Harare, Zimbabwe
                Author notes
                [& ]Corresponding author: Nyasha Chin'ombe, Department of Medical Microbiology, College of Health Sciences, University of Zimbabwe, P O Box A178, Avondale, Harare, Zimbabwe
                Article
                Publisher ID: PAMJ-20-386
                DOI: 10.11604/pamj.2015.20.386.4660
                PMC ID: 4499268
                PubMed ID: 26185576
                SO-VID: df71ca5a-412a-44ec-a7ac-2f05ed7739cd
                Copyright © © Nyasha Chin'ombe et al.
                License:

                The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 May 2014
                Date accepted : 13 April 2015
                Categories
                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: hiv/aids,vaccines,africa
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: hiv/aids, vaccines, africa

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