Search

Tuberculosis (TB) is a global public health problem exacerbated by the HIV epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in HIV-infected adults in Senegal. 24 patients were enrolled: Group 1∶12, antiretroviral therapy (ART) naïve, adults, with CD4 counts >300 and HIV RNA load <100 000 copies/ml. Group 2∶12 adults, stable on ART, with CD4 counts >300, and an undetectable HIV RNA load. Safety was evaluated by occurrence of local and systemic adverse events (AEs) and by monitoring of CD4 count, HIV RNA load, haematology and biochemistry. Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay. 87.7% of AEs were mild; 11.6% were moderate; and 0.7% were severe. 29.2% of AEs were systemic; 70.8% were expected local AEs. There were no vaccine-related Serious Adverse Events (SAEs) or clinically significant effects on HIV RNA load or CD4 count. In ART naive subjects, the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation, which contracted to baseline by 12 weeks. Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination. A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects. Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects; responses were comparable after 2 immunisations. In conclusion, MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal. A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART. Clinicaltrials.gov trial identifier NCT00731471. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum is an intracellular protozoan parasite that infects erythrocytes and hepatocytes. The blood stage of its life cycle causes substantial morbidity and mortality associated with millions of infections each year, motivating an intensive search for potential components of a multi-subunit vaccine. In this study, we present data showing that antibodies from natural infections can recognize a recombinant form of the relatively conserved merozoite surface antigen, PfRH5. Furthermore, we performed invasion inhibition assays on clinical isolates and laboratory strains of P. falciparum in the presence of affinity purified antibodies to RH5 and show that these antibodies can inhibit invasion in vitro. [ABSTRACT FROM AUTHOR]

Killer immunoglobulin-like receptors (KIRs) regulate natural killer (NK) cells in a human leukocyte antigen (HLA)-dependent manner. KIR/HLA mismatched hematopoietic stem cell transplants induce alloreactive NK cells, which prevent leukemia relapse. Certain KIR/HLA combinations protect against HIV-1 infection, but the effect of KIR/HLA mismatches between sexual partners has never been investigated. In this study, we analyzed the effect of allogeneic KIR/HLA combinations on HIV-1 transmission in a West African population of HIV-1-discordant and concordant couples. HIV-1-discordant couples were characterized by recipient partners with homozygous KIR2DL2, and by a mismatched recipient partner KIR2DL 1/HLA-C2 with index partner HLA-C1/C1 combination expected to allow licensed missing self NK cell killing of index partners' cells. HIV-1-concordant couples on the other hand were characterized by KIR2DL3 homozygous recipient partners with HLA-C1/C2 bearing index partners, resulting in a matched KIR/HLA combination expected to inhibit NK cell killing. In vitro cocultures of healthy donor-derived NK cells and HIV-1 patient-derived CD4+ T cells confirmed the involvement of these allogeneic KIR/HLA combinations in NK cell-mediated CD4+ T-cell killing. Our data suggest that KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission and that this may be due to alloreactive NK cell killing of the HIV-1-infected partner's cells. (Blood.2013;121(7):1157-1164) [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) has been shown to accelerate the clinical course of HIV infection, but the mechanisms by which this occurs are not well understood. Regulatory T-cells (Tregs) are known to dampen hyperactivation of the immune cells, but it remains unclear whether hyperactivation of T-cells in HIV infection is associated with a decrease of Tregs and what the effect Mycobacterium tuberculosis (MTB) co-infection has on T-cell activation and Tregs. Objectives: In this study, we aim to evaluate whether active TB is associated with the increased expression of T-cell activation markers and reduced number of Treg cells in HIV-1-infected patients. Methods: This study was conducted on 69 subjects consisting of 20 HIV-infected patients, 20 HIV and MTB co-infected patients, 19 MTB-infected patients and 10 uninfected control subjects negative for both MTB and HIV. The frequencies of T-cell activation markers (CD38 and HLA-DR) and Treg cells (CD4+CD25+CD127-) were measured by flow cytometry. Results: Significantly higher expression of CD38 and HLA-DR on CD4+ and CD8+ T-cells was found in MTB and HIV co-infected patients compared with HIV-infected patients. However, no significant difference in the percentage of Treg cells was reported between HIV patients with TB and those without. The study also showed a negative correlation between regulatory T-cells frequency and CD4+ T-cell counts. Conclusion: These results suggest that TB enhances the expression of peripheral T-cell activation markers during HIV infection, whilst having no impact on the percentages of Treg cells. [ABSTRACT FROM AUTHOR]

Background. Schistosome infections are often clinically silent, but some individuals develop severe pathological reactions. In several disease processes, T-helper 17 (Th17) cells have been linked to tissue injuries, while regulatory T cells (Tregs) are thought to downmodulate inflammatory reactions. We assessed whether bladder pathology in human Schistosoma haematobium infection is related to the balance of Th17 cells and Tregs. We used a murine model of Schistosoma mansoni infection to further investigate whether the peripheral profiles reflected ongoing events in tissues.Methods. We characterized T-helper cell subsets in the peripheral blood of children residing in a S. haematobium–endemic area and in the peripheral blood, spleen, and hepatic granulomas of S. mansoni–infected high-pathology CBA mice and low-pathology C57BL/6 mice.Results. S. haematobium–infected children with bladder pathology had a significantly higher percentage of Th17 cells than those without pathology. Moreover, the Th17/Treg ratios were significantly higher in infected children with pathology, compared with infected children without pathology. Percentages of interleukin 17–producing cells were significantly higher in spleen and granulomas of CBA mice, compared with C57BL/6 mice. This difference was also reflected in the peripheral blood.Conclusions. This is the first study to indicate that Th17 cells may be involved in the pathogenesis of human schistosomiasis. [ABSTRACT FROM AUTHOR]

Abstract: With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: (1) studies of the entire population (that are not restricted to children ≤5 or ≤10 years of age), (2) study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and (3) innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases. [Copyright &y& Elsevier]

A response from the authors of the article "KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission" in the February 14, 2013 issue is presented.