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At least 595 records · Page 33Linked to original sources
PubMed2001

Update on HIV patient management: latest trends in laboratory testing, immune cell reconstitution, and vaccine development.

HIV patient management requires the close interaction of clinicians and laboratorians to integrate the results obtained by emerging methodologies. Evaluation of drug susceptibility to screen for specific mutations in the HIV genome can avoid needless treatment with ineffective drugs, maximizing the benefits of costly triple-drug therapy. In addition, providing a scientific basis for the effective use of genotyping and therapeutic drug monitoring is a valuable role that laboratorians can play in optimizing patient care. The clinical utility of HIV genotyping has been defined more clearly during the last year, and pharmacokinetic profiles of the antiretrovirals are beginning to emerge in the clinical laboratory as a tool to periodically assess adherence to and efficacy of the drug regimens. However, much more work is required in this area. Switching to simpler regimens is perceived as a means to improve medication adherence, manage drug toxicity, and reduce the potential for interaction among different drugs. HIV affects the function of both cytotoxic T-cells and neutralizing antibodies. The ability to identify and quantify HIV-specific immunity may allow us to target and expand specific deficient cell clones as a means of correcting immune deficiencies and strengthening the effects of drug therapy. One such example is IL-2, shown to increase CD4 cell counts at various stages of HIV disease. Additional studies of IL-2 therapy and newer immune modulators are ongoing. Combination vaccines are being tested as a worthwhile approach to optimize induction of both CTLs and antibodies. The role of the laboratory to determine the potency of HIV vaccine candidates awaits further developments evaluating the relative importance of neutralizing and mucosal antibodies versus CTL responses and the degree of immunogenicity needed to contain the spread of infection. The Center for Disease Control and Prevention aims to reduce new HIV infections by 50% per year in the next five years, and this goal is to be achieved through selected strategies put together by the plethora of experts in this arena. The aim of this article is to update the reader on the latest trends in HIV patient management and motivate collaborations to assist in the prompt implementation of improved medical care.

Journal Article↗
PubMed2006

Human dendritic cell interactions with whole recombinant yeast: implications for HIV-1 vaccine development.

Defects in number and function of dendritic cells (DCs) have been observed during HIV-1 infection, so therapeutic HIV-1 vaccine approaches that target or activate DCs may improve vaccine immunogenicity. To determine the potential of recombinant Saccharomyces cerevisiae yeast as an HIV-1 vaccine, we investigated interactions between yeast and human DCs. Yeast induced direct phenotypic maturation of monocyte-derived DCs (MDDCs) and enriched blood myeloid DCs (mDCs), but only indirectly matured blood plasmacytoid DCs (pDCs). Yeast-pulsed MDDCs and blood mDCs produced inflammatory cytokines and stimulated strong allo-reactive T cell proliferation. Both blood DC subsets internalized yeast, and when pulsed with yeast recombinant for HIV-1 Gag protein, both stimulated in vitro expansion of Gag-specific CD8+ memory T cells. These results suggest that S. cerevisiae yeast have potent adjuvant effects on human DCs. Furthermore, recombinant yeast-derived antigens are processed by human blood DCs for MHC class-I cross-presentation. These DC-targeting characteristics of yeast suggest that it may be an effective vaccine vector for induction of HIV-1-specific cellular immune responses.

AIDS Vaccines↗
PubMed2000

Immune response against Mycobacterium tuberculosis: implications for vaccine development.

Tuberculosis remains a major health problem globally. Although this threat would best be controlled by a combination of chemotherapy and vaccination, satisfactory vaccines are not available yet. Rational design of a novel vaccine generation against tuberculosis has become possible on the basis of recent achievements in molecular genetics of the pathogen and immunology of the host. Currently, two different strategies are pursued. First, the subunit vaccine approach attempting to induce efficacious immunity by unique antigens in defined adjuvants. Second, the whole bacterial vaccine approach relying on multiple antigens and built-in adjuvanticity. Time will tell which type of vaccine is best suited for eradication of tuberculosis.

Bacterial Vaccines↗
PubMed1990

Antigen delivery systems for analysing host immune responses and for vaccine development.

Overall, the meeting was timely and worthwhile. It is evident that there is a need for comparative studies to establish a firm foundation for future work. This is particularly important since it appears that the responses observed are influenced by the particular strain used for attenuation, the means of attenuation, the antigen-presentation system employed and the animal most immunized. In this last regard, one must recognize that most work to date has been with inbred strains of mice which differ from the genetic diversity of most hosts that are the intended beneficiaries of the immunization strategies being developed.

Animals↗
PubMed1998

Genetic variation of HIV type 1: relevance of interclade variation to vaccine development.

Accumulating data in human immunodeficiency virus (HIV)-infected individuals support the hypothesis that in primary human immunodeficiency virus type 1 (HIV-1) isolates of different clades and phenotype (syncytium inducing [SI] and nonsyncytium inducing [NSI]) common antigenic structures must exist that can stimulate the immune response to produce a broad spectrum (cross-clade and cross SI and NSI) neutralization response. Certain vaccination regimens in chimpanzees and human volunteers with clade B SI type HIV-1 derived candidate vaccines induce neutralizing antibodies against intraclade B SI type primary HIV-1 isolates, but not against intraclade B NSI type of viruses. To be effective against the full antigenic spectrum of primary HIV-1 isolates (cross-clade--SI and NSI) candidate vaccines should contain immunogens of primary isolates representative of the whole antigenic spectrum of HIV-1. There is an urgent need to identify these immunogens and to improve their immunogenicity. As long as we have not yet characterized these cross-HIV-1 spectrum conserved immunogens, candidate vaccines against the more prevalent clades C, A, and E should be developed for evaluation in developing countries. In support of the follow-up and evaluation of the hopefully increasing number of phase 1, 2, and 3 HIV-1 vaccine trials in humans, it is considered a high priority to develop a high throughput neutralization assay, to further expand the use of a limited number of key primary HIV-1 isolates as a surrogate for neutralization of the entire HIV-1 antigenic spectrum (cross-clade--SI and NSI), to develop high throughput subtyping as well as a rapid system to monitor the immunogenic relatedness of different HIV-1 clades.

AIDS Vaccines↗
PubMed2003

How far have we reached in tuberculosis vaccine development?

Tuberculosis, a bacterial disease prevalent since ancient times, continues to cause the most deaths globally compared with all other diseases. The causative agent Mycobacterium tuberculosis is responsible for different types of tuberculosis in humans; however, pulmonary tuberculosis is the most common and causes the most deaths. Mycobacterium tuberculosis is an intracellular pathogenic bacterium, which has developed sophisticated mechanisms to survive inside host mononuclear phagocytes and thus evade the host immune system. This is attributed primarily to an inadequate immune response toward infecting bacteria, which results in temporary growth inhibition rather than death and subsequently allows the bacteria to multiply immensely, leading to full-blown disease in an individual. This disease has become a challenge due to poor diagnosis, a low-efficiency tuberculosis vaccine (Mycobacterium bovis Bacillus Calmette-Guerin [BCG]), a long-term antibacterial chemotherapy regimen (approximately 6 months), and an emergence of multiple drug resistant strains of Mycobacterium tuberculosis especially in people with human immune deficiency virus (HIV) infection, for whom researchers worldwide must develop effective short-term chemotherapy and an effective vaccine. In this review different aspects of vaccines in tuberculosis are discussed, and these include the traditional BCG vaccine, the modern auxotrophic vaccine, the subunit or acellular vaccine; and a DNA vaccine. We discuss also the potential of mycobacterial lipids as a vaccine or as an adjuvant in the future. Since complete genome information of Mycobacterium tuberculosis H37Rv and bioinformatics tools are available, it is possible to develop new strategies for a better and effective tuberculosis vaccine, which can replace the traditional BCG vaccine.

Animals↗
PubMed1999

Conserved hepatitis C virus sequences are highly immunogenic for CD4(+) T cells: implications for vaccine development.

The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.

Acute Disease↗