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HIV Vaccine (hiv + vaccine)
Selected AbstractsImpact of the international program for quality assessment and standardization for immunological measures relevant to HIV/AIDS: QASICYTOMETRY, Issue 2 2002Francis Mandy Abstract Measurements of CD4 T-cell levels are essential for the assessment of human immunodeficiency virus (HIV) disease course, clinical staging, epidemiological studies, and decisions regarding prophylactic therapies against opportunistic infection. Until now, only in the industrialized countries was T-cell subset monitoring considered a practical option to assess disease progression. The Quality Assessment and Standardization for Immunological Measures Relevant to HIV/AIDS (QASI) program was established in 1997 to meet performance assessment for immunophenotyping laboratories in countries where such service is not available. The QASI program is provided at no cost to any laboratory in a resource-poor setting that wishes to participate. This report describes the beneficial impact of participation in the QASI program. Carefully selected commercial stabilized whole blood preparations were sent regularly to participating laboratories. Participants reported the T-cell subset values they obtained by flow cytometry. Once the aggregate mean values for the T-cell subsets were established for the shipment, a comprehensive and confidential report was sent to each laboratory. The results from five consecutive shipments were analyzed. The coefficient of variation decreased from 7.2% to 4.7% and from 14.2% to 8.8% for percent and absolute CD4 T-cell counts, respectively. With the implementation of the QASI program using commercial stabilized whole blood specimens, it is possible to reduce interlaboratory error. This study illustrates that a quality assessment program can improve the overall performance of laboratories. Reducing interlaboratory variation can enhance significantly the effectiveness of multicenter HIV vaccine or drug trial evaluation. Cytometry (Clin. Cytometry) 50:111,116, 2002. © 2002 Wiley-Liss, Inc. [source] Highly avid, oligoclonal, early-differentiated antigen-specific CD8+ T cells in chronic HIV-2 infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2010Aleksandra Leligdowicz Abstract HIV-1-specific CD8+ T cells are present in most HIV-1-infected people and play an important role in controlling viral replication, but the characteristics of an effective HIV-specific T-cell response are largely unknown. The majority of HIV-2-infected people behave as long-term non-progressors while those who progress to AIDS do so in a manner indistinguishable from HIV-1. A detailed study of HIV-2 infection may identify protective immune responses. Robust gag p26-specific T-cell responses are elicited during HIV-2 infection and correlate with control of viremia. In this study, we analyzed features of an HLA-B*3501-restricted T-cell response to HIV-2 p26 that may contribute to virus control. In contrast to HIV-1, HIV-2-specific T cells are at an early stage of differentiation (CD27+CD28+), a finding that relates directly to CD4+ T-cell levels and inversely to immune activation. The cells demonstrate IFN-, secretion, oligoclonal T-cell receptor V, gene segment usage, exceptional avidity and secretion of pro-inflammatory cytokines. Despite the potentially strong selection pressure imposed on the virus by these cells, there was no evidence of HIV-2 sequence evolution. We propose that in chronic HIV-2 infection, the maintenance of early-differentiated, highly avid CD8+ T cells could account for the non-progressive course of disease. Such responses may be desirable from an HIV vaccine. [source] Is the Salk principle still viable for the design of an effective HIV vaccine?HIV MEDICINE, Issue 5 2004JD Lundgren No abstract is available for this article. [source] Developing an HIV cytotoxic T-lymphocyte vaccine: issues of CD8 T-cell quantity, quality and locationJOURNAL OF INTERNAL MEDICINE, Issue 1 2009D. Masopust Abstract. Issues of quantity, quality and location impact the ability of CD8 T cells to mediate protection from infection. These issues are considered in light of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccination. Methods are reviewed that result in 100- to 1000-fold higher frequencies of vaccine-specific memory CD8 T cells than that achieved by current HIV/SIV vaccine approaches. Data demonstrating that location within mucosal tissues has a direct impact on memory CD8 T-cell function are discussed. Arguments are made that establishing memory CD8 T cells within mucosal sites of transmission, a priori to natural infection, may be essential for conferring optimal and rapid protection. Lastly, it is proposed that heterologous prime-boost vaccination with recombinant live replicating vectors, which has the potential to induce tremendous numbers of cytolytic memory CD8 T cells within mucosal tissues, would provide a far more stringent test of the hypothesis that memory CD8 T cells could, in principal, form the basis for a preventative HIV vaccine. [source] A review of vaccines for HIV preventionTHE JOURNAL OF GENE MEDICINE, Issue 1 2003Matilu Mwau Abstract HIV/AIDS has become the most devastating pandemic in recorded history. It has killed 40 million people in the last 20 years and the World Health Organisation estimated that at least 14 000 new infections occurred daily in 2001. There will be up to 100 million new infections in the next 10 years (for current updates, visit http://www.unaids.org/epidemic_update/). Most HIV infections occur in the developing world, and the adverse social and economic impact of the HIV/AIDS pandemic, particularly in the developing world, is unprecedented. Highly active antiretroviral therapy (HAART) has had significant effects on HIV/AIDS in the developed world. The drugs have acted to prolong survival, reduce the viral load, and to alleviate suffering. However, the incidence of side effects and resistance is high and the drugs are unaffordable and unavailable in the developing world. HAART regimens are difficult to comply with. Public health efforts to modify the behaviour, attitude and culture that accelerate the spread of HIV/AIDS have had only modest success. There is urgent need for a prophylactic and/or therapeutic HIV vaccine. This is a review of the obstacles and current trends in HIV vaccine development. Copyright © 2002 John Wiley & Sons, Ltd. [source] A Comparison of Eight Methods for the Dual-Endpoint Evaluation of Efficacy in a Proof-of-Concept HIV Vaccine TrialBIOMETRICS, Issue 3 2006Devan V. Mehrotra Summary To support the design of the world's first proof-of-concept (POC) efficacy trial of a cell-mediated immunity-based HIV vaccine, we evaluate eight methods for testing the composite null hypothesis of no-vaccine effect on either the incidence of HIV infection or the viral load set point among those infected, relative to placebo. The first two methods use a single test applied to the actual values or ranks of a burden-of-illness (BOI) outcome that combines the infection and viral load endpoints. The other six methods combine separate tests for the two endpoints using unweighted or weighted versions of the two-part z, Simes', and Fisher's methods. Based on extensive simulations that were used to design the landmark POC trial, the BOI methods are shown to have generally low power for rejecting the composite null hypothesis (and hence advancing the vaccine to a subsequent large-scale efficacy trial). The unweighted Simes' and Fisher's combination methods perform best overall. Importantly, this conclusion holds even after the test for the viral load component is adjusted for bias that can be introduced by conditioning on a postrandomization event (HIV infection). The adjustment is derived using a selection bias model based on the principal stratification framework of causal inference. [source] Strategies for optimizing targeting and delivery of mucosal HIV vaccinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2009Jeffrey D. Ahlers Abstract Effective frontline defenses against HIV-1 will require targeting vaccines to mucosal tissue in order to induce ,, CD8+ lymphocytes in mucosal effector sites (lamina propria and intraepithelial compartment) as well as antibody secreting plasma cells that can neutralize and limit free virus. A concerted second wave of assault against the virus will require the activation and recruitment of antigen specific memory CD4+ and CD8+ T cells in mesenteric lymph nodes and distal secondary lymphoid organs. New delivery strategies targeting the "right" DC subsets in combination with delivery of mucosal adjuvants and innate signals for activating DC will be essential for mucosal vaccines in order to circumvent the naturally tolerogenic environment and the induction of Tregs. Mucosal delivery of antigen in combination with inflammatory signals has been shown to empower systemic immunization by directing responses to mucosal sites for imprinting optimum mucosal memory. Here, we discuss novel vaccine strategies and adjuvants for optimizing mucosal delivery of HIV vaccines. [source] Efficient mucosal delivery of the HIV-1 Tat protein using the synthetic lipopeptide MALP-2 as adjuvantEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Stefan Borsutzky Abstract A major requirement for HIV/AIDS research is the development of a mucosal vaccine that stimulates humoral and cell-mediated immune responses at systemic and mucosal levels, thereby blocking virus replication at the entry port. Thus, a vaccine prototype based on biologically active HIV-1 Tat protein as antigen and the synthetic lipopeptide, macrophage-activating lipopeptide-2 (MALP-2), asa mucosal adjuvant was developed. Intranasal administration to mice stimulated systemic and mucosal anti-Tat antibody responses, and Tat-specific T cell responses, that were more efficient than those observed after i.p. immunization with Tat plus incomplete Freund's adjuvant. Major linear B cell epitopes mapped within aa 1,20 and 46,60, whereas T cell epitopes were identified within aa 36,50 and 56,70. These epitopes have also been described in vaccinated primates and in HIV-1-infected individuals with better prognosis. Analysis of the anti-Tat IgG isotypes in serum, and the cytokine profile of spleen cells indicated that a dominant Th1 helper response was stimulated by Tat plus MALP-2, as opposed to the Th2 response observed with Tat plus incomplete Freund's adjuvant. Tat-specific IFN-,-producing cells were significantly increased only in response to Tat plus MALP-2. These data suggest that Malp-2 may represent an optimal mucosal adjuvant for candidate HIV vaccines based on Tat alone or in combination with other HIV antigens. [source] Assessing Vaccine Effects in Repeated Low-Dose Challenge ExperimentsBIOMETRICS, Issue 4 2009Michael G. Hudgens Summary Evaluation of HIV vaccine candidates in nonhuman primates (NHPs) is a critical step toward developing a successful vaccine to control the HIV pandemic. Historically, HIV vaccine regimens have been tested in NHPs by administering a single high dose of the challenge virus. More recently, evaluation of candidate HIV vaccines has entailed repeated low-dose challenges, which more closely mimic typical exposure in natural transmission settings. In this article, we consider evaluation of the type and magnitude of vaccine efficacy from such experiments. Based on the principal stratification framework, we also address evaluation of potential immunological surrogate endpoints for infection. [source] | |||||||||||||