HIV vaccine research: The way forward

National Institute of Allergy and Infectious Diseases, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892, USA.
Science (Impact Factor: 33.61). 07/2008; 321(5888):530-2. DOI: 10.1126/science.1161000
Source: PubMed


The need to broaden research directed at answering fundamental questions in HIV vaccine discovery through laboratory, nonhuman primate (NHP), and clinical research has recently been emphasized. In addition, the importance of attracting and retaining young researchers, developing better NHP models, and more closely linking NHP and clinical research is being stressed. In an era of a level budget for biomedical research at the U.S. National Institutes of Health (NIH), HIV/AIDS vaccine research efforts will need to be carefully prioritized such that resources to energize HIV vaccine discovery can be identified. This article summarizes progress and challenges in HIV vaccine research, the priorities arising from a recent summit at NIAID, and the actions needed, some already under way, to address those priorities.

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    • "In 2004, a Phase IIb trial with Merck's MRKAd5, which is a trivalent vaccine including gag, pol, and nef genes in an adenovirus 5 vector, is designed for inducing cytotoxic T cell responses [9, 10]. Despite the induction of significant level of IFN gamma-producing T cells, the MRKAd5 has increased the risk of HIV acquisition in vaccine recipients and failed to reduce viral load after HIV infection [11]. Later in 2009, a Phase III trial of RV144 HIV-1 vaccine was completed in Thailand, which is a vaccine combination comprised of ALVAC (a vaccine containing genetically engineered versions of gag, env, and pol inserted in canarypox vector) and AIDSVAX (a bivalent gp120 envelope protein vaccine). "
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    ABSTRACT: CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese.
    BioMed Research International 07/2014; 2014(1):272950. DOI:10.1155/2014/272950 · 1.58 Impact Factor
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    • "This is especially the case for women because of the increasing feminization of the pandemic epicenter in sub-Saharan Africa where 75 percent of the HIV-1 infected population ages 15–24 are females [1], [2]. Development of a prophylactic vaccine to prevent HIV infection represents the most effective, economical, and universal solution to achieving this goal, but thus far in human trials, vaccine candidates have been at best marginally effective [3], [4]. The SIV-infected rhesus macaque model of HIV is a powerful system being used to gain insights into HIV/SIV pathogenesis and aid in the development of an effective HIV vaccine. "
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    ABSTRACT: Live-attenuated SIV vaccines (LAVs) have been the most effective to date in preventing or partially controlling infection by wild-type SIV in non-human primate models of HIV-1 transmission to women acting by mechanisms of protection that are not well understood. To gain insights into mechanisms of protection by LAVs that could aid development of effective vaccines to prevent HIV-1 transmission to women, we used in situ tetramer staining to determine whether increased densities or changes in the local distribution of SIV-specific CD8 T cells correlated with the maturation of SIVΔnef vaccine-induced protection prior to and after intra-vaginal challenge with wild-type SIVmac251. We evaluated the immunodominant Mamu-A1*001:01/Gag (CM9) and Mamu-A1*001:01/Tat (SL8) epitope response in genital and lymphoid tissues, and found that tetramer+ cells were present at all time points examined. In the cervical vaginal tissues, most tetramer+ cells were distributed diffusely throughout the lamina propria or co-localized with other CD8 T cells within lymphoid aggregates. The distribution and densities of the tetramer+ cells at the portal of entry did not correlate with the maturation of protection or change after challenge. Given these findings, we discuss the possibility that changes in other aspects of the immune system, including the quality of the resident population of virus-specific effector CD8 T cells could contribute to maturation of protection, as well as the potential for vaccine strategies that further increase the size and quality of this effector population to prevent HIV-1 transmission.
    PLoS ONE 12/2013; 8(12):e81623. DOI:10.1371/journal.pone.0081623 · 3.23 Impact Factor
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    • "Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has become the most catastrophic pandemic since first discovered in 1981. To date, more than 300,000 people have died of HIV/AIDS, with approximately 6500 new infections daily.1 After years of efforts, though we have seen dramatic progress in treating HIV, it is still difficult to eradicate the virus.2 "
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    ABSTRACT: The heterologous deoxyribonucleic acid (DNA) prime-adenovirus (AdV) boost vaccination approach has been widely applied as a promising strategy against human immunodeficiency virus (HIV)-1. However, the problem of inefficient delivery and lack of specificity of DNA vaccine remains a major issue. In this paper, to improve the transfection of DNA vaccine and realize dendritic cell targeting, we used mannosylated polyethyleneimine (man-PEI) as a DNA vector carrier. The DNA plasmid encoding antigen HIV gag fragment was constructed by polymerase chain reaction. Then the DNA plasmid was complexed with man-PEI. The in vitro transfection efficiency of man-PEI/DNA was analyzed on DC 2.4 cells. Mice were primed with 25 μg pVAX1-HIV gag plasmid complexed with man-PEI, 100 μg naked pVAX1-HIV gag plasmid, or empty pVAX1 vector and boosted by AdV encoding the same antigen. The antibody titer, CD4(+) and CD8(+) T-cell response, as well as interferon-γ and interleukin-4 levels in serum and in splenocytes culture were analyzed using flow cytometry or enzyme-linked immunosorbent assay to evaluate the immune response. To test a long-term effect of the vaccination regimen, CD8(+) memory T-cell was also detected by flow cytometry. The pVAX1-HIV gag was constructed successfully. The in vitro transfection efficiency in dendritic cells was significantly higher than naked DNA plasmid. Compared with 100 μg naked DNA/AdV group, the immunoglobulin G2a antibody titer, T-cell response percentage, and cytokine production level induced by man-PEI/DNA/AdV group were significantly higher at a lower DNA dose. Also, the man-PEI/DNA could stimulate a memory CD8(+) T-cell response. Owing to the adjuvant effect of man-PEI, the man-PEI/pVAX1-HIV gag priming plus AdV boosting strategy proved to be a potent vaccine candidate against HIV, which could induce a stronger immune response with a lower DNA dose.
    International Journal of Nanomedicine 05/2013; 8:1843-1854. DOI:10.2147/IJN.S43827 · 4.38 Impact Factor
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