Peptide immunogens provide an approach to focus antibody responses to specific neutralizing sites on the HIV envelope protein (Env) trimer or on other pathogens. However, the physical characteristics of peptide immunogens can limit their pharmacokinetic and immunological properties. Here, we have designed synthetic "star" nanoparticles based on biocompatible N-[(2-hydroxypropyl)methacrylamide] (HPMA)-based polymer arms extending from a poly(amidoamine) (PAMAM) dendrimer core. In mice, these star nanoparticles trafficked to lymph nodes (LNs) by 4 hours following vaccination, where they were taken up by subcapsular macrophages and then resident dendritic cells (DCs). Immunogenicity optimization studies revealed a correlation of immunogen density with antibody titers. Furthermore, the co-delivery of Env variable loop 3 (V3) and T-helper peptides induced titers that were 2 logs higher than if the peptides were given in separate nanoparticles. Finally, we performed a nonhuman primate (NHP) study using a V3 glycopeptide minimal immunogen that was structurally optimized to be recognized by Env V3/glycan broadly neutralizing antibodies (bnAbs). When administered with a potent Toll-like receptor (TLR) 7/8 agonist adjuvant, these nanoparticles elicited high antibody binding titers to the V3 site. Similar to human V3/glycan bnAbs, certain monoclonal antibodies (mAbs) elicited by this vaccine were glycan dependent or targeted the GDIR peptide motif. To improve affinity to native Env trimer affinity, nonhuman primates (NHPs) were boosted with various SOSIP Env proteins; however, significant neutralization was not observed. Taken together, this study provides a new vaccine platform for administration of glycopeptide immunogens for focusing immune responses to specific bnAb epitopes.
- MeSH
- epitopy imunologie MeSH
- HIV infekce imunologie MeSH
- HIV obalový protein gp120 chemie MeSH
- HIV séropozitivita imunologie MeSH
- HIV-1 imunologie MeSH
- Macaca mulatta MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nanočástice chemie terapeutické užití MeSH
- neutralizující protilátky imunologie MeSH
- peptidy MeSH
- primáti MeSH
- tvorba protilátek imunologie MeSH
- vakcíny proti AIDS imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
- Klíčová slova
- denzita kostního minerálu,
- MeSH
- fraktury kostí * farmakoterapie metabolismus patologie prevence a kontrola MeSH
- HIV séropozitivita * diagnóza imunologie komplikace metabolismus terapie MeSH
- kombinovaná farmakoterapie metody MeSH
- kostní denzita fyziologie MeSH
- lidé MeSH
- metaanalýza jako téma MeSH
- metabolické nemoci kostí epidemiologie etiologie prevence a kontrola terapie MeSH
- osteoporóza epidemiologie etiologie prevence a kontrola terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
OBJECTIVES: To determine the incidence and laboratory characteristics of primary Toxoplasma gondii infection in HIV-infected individuals. METHODS: This retrospective study was conducted between 1988 and 2012 on a cohort of 1130 HIV-infected patients at the AIDS Center Prague. Toxoplasma serology, standard laboratory parameters, and health status were evaluated at 3-6-month intervals for all patients. RESULTS: The total person-time of follow-up of patients at risk of Toxoplasma seroconversion was 3046.3 years; there were 14 primary T. gondii infections, yielding an incidence rate of 0.0046 (95% confidence interval 0.0027-0.0078). Most of the subjects were clinically asymptomatic, but in one case seroconversion was accompanied by transient cervical lymphadenopathy. The CD4+ T-lymphocyte count geometric mean increased from 418 (95% confidence interval 303-579) cells/μl before seroconversion to 501 (95% confidence interval 363-691) cells/μl after seroconversion (p = 0.004), while other parameters (CD8+ T-lymphocytes, natural killer cells, viral load, beta2-microglobulin, total immunoglobulins) remained unchanged. As compared to the control group, patients with primary toxoplasmosis had higher initial levels of total immunoglobulins IgA and IgG and a tendency to higher CD8+ T lymphocyte counts. CONCLUSIONS: Neither the incidence nor the course of the primary Toxoplasma infection was influenced by the immune status of the patients. Immune parameters of patients with primary Toxoplasma infection did not differ from those of the controls.
- MeSH
- dospělí MeSH
- HIV protilátky krev MeSH
- HIV séropozitivita epidemiologie imunologie MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- oportunní infekce doprovázející AIDS epidemiologie imunologie MeSH
- počet CD4 lymfocytů MeSH
- retrospektivní studie MeSH
- toxoplazmóza epidemiologie imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Human immunodeficiency virus type 1 (HIV-1) entry is mediated by the interaction between a variably glycosylated envelope glycoprotein (gp120) and host-cell receptors. Approximately half of the molecular mass of gp120 is contributed by N-glycans, which serve as potential epitopes and may shield gp120 from immune recognition. The role of gp120 glycans in the host immune response to HIV-1 has not been comprehensively studied at the molecular level. We developed a new approach to characterize cell-specific gp120 glycosylation, the regulation of glycosylation, and the effect of variable glycosylation on antibody reactivity. A model oligomeric gp120 was expressed in different cell types, including cell lines that represent host-infected cells or cells used to produce gp120 for vaccination purposes. N-Glycosylation of gp120 varied, depending on the cell type used for its expression and the metabolic manipulation during expression. The resultant glycosylation included changes in the ratio of high-mannose to complex N-glycans, terminal decoration, and branching. Differential glycosylation of gp120 affected envelope recognition by polyclonal antibodies from the sera of HIV-1-infected subjects. These results indicate that gp120 glycans contribute to antibody reactivity and should be considered in HIV-1 vaccine design.
- MeSH
- AIDS imunologie MeSH
- buněčné linie MeSH
- buňky Hep G2 metabolismus MeSH
- ELISA metody MeSH
- glykosidhydrolasy metabolismus MeSH
- glykosylace MeSH
- HIV obalový protein gp120 genetika imunologie izolace a purifikace metabolismus MeSH
- HIV séropozitivita imunologie metabolismus MeSH
- HIV-1 imunologie metabolismus MeSH
- hmotnostní spektrometrie MeSH
- Jurkat buňky metabolismus MeSH
- komplementární DNA genetika MeSH
- lektin vázající mannosu genetika MeSH
- lidé MeSH
- mannosa metabolismus MeSH
- nádorové buněčné linie MeSH
- oligosacharidy chemie izolace a purifikace MeSH
- plazmidy MeSH
- polysacharidy chemie izolace a purifikace MeSH
- protilátky imunologie MeSH
- specificita protilátek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
This is to appreciate of truthness of predicate, that HIV-positive patients have, in most cases, the chance to develop postoperative complications and unsuccessful results. In the study, we assessed the experience of the first author in 3 years of expert work in Botswana, Southern Africa, and used nonparametric tests for statistical assessment of the results in those patients. In addition to clinical follow-up are patients assessed through study of CD4+ T lymphocytes and CD8+ T lymphocytes levels. Only in the most serious immunodeficiency group (Group C) were statistically important deviations in deaths and complications of wounds and anastomoses healing. For example, comparing HIV-positive patients and the HIV-negative population using a CD4+ T-lymphocyte level < 200 mm3, we can see the differences in the mortality rate: HIV-positive patients, 23.96%; HIV negative population 8.11%. The complication rate in HIV-positive patients with a CD4 level < 200 mm3 was 38.54% and in the HIV-negative population was 9.46%. The study disputes the myth that, in the majority of HIV-positive patients, we can expect limited surgical results and a larger rate of deaths and complications in wounds and anastomoses healing.
- MeSH
- anastomóza chirurgická MeSH
- CD4-pozitivní T-lymfocyty MeSH
- CD8-pozitivní T-lymfocyty MeSH
- dospělí MeSH
- HIV séropozitivita imunologie MeSH
- hojení ran imunologie MeSH
- hostitel s imunodeficiencí MeSH
- lidé středního věku MeSH
- lidé MeSH
- neparametrická statistika MeSH
- pooperační komplikace imunologie mortalita MeSH
- prospektivní studie MeSH
- rozdělení chí kvadrát MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Jihoafrická republika MeSH
- MeSH
- antifosfolipidové protilátky analýza imunologie krev MeSH
- antigeny CD4 analýza MeSH
- antigeny CD8 analýza MeSH
- finanční podpora výzkumu jako téma MeSH
- HIV séropozitivita imunologie MeSH
- lidé MeSH
- vysoce aktivní antiretrovirová terapie metody využití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kongresy MeSH
- MeSH
- biologické markery MeSH
- HIV séropozitivita imunologie MeSH
- lidé MeSH
- nádory imunologie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- WOBENZYM,
- MeSH
- antigeny CD4 MeSH
- dospělí MeSH
- enzymoterapie MeSH
- enzymy aplikace a dávkování škodlivé účinky MeSH
- HIV séropozitivita enzymologie farmakoterapie imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- proteasy farmakologie terapeutické užití MeSH
- T-lymfocyty účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- ELISA MeSH
- HIV séropozitivita imunologie MeSH
- imunoglobulin G MeSH
- imunoglobulin M MeSH
- lidé MeSH
- protilátky bakteriální MeSH
- tuberkulóza imunologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
