OBJECTIVES: To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. STUDY DESIGN: We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. METHODS: We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. RESULTS: p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. CONCLUSION: Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.

AIDS Vaccines↗

PubMedDate not supplied

Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.

OBJECTIVES: To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. METHOD: The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). RESULTS: Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. CONCLUSION: These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.

AIDS Vaccines↗

PubMedDate not supplied

Human papillomavirus-16-E7 oncoprotein enhances the expression of adhesion molecules in cervical endothelial cells but not in human umbilical vein endothelial cells.

OBJECTIVES: E7 is one of the oncoproteins encoded by human papillomavirus-16 (HPV-16), the major etiologic factor responsible for cervical cancer. Human papillomavirus-16-E7 expressed by human uterine cervix carcinoma cells is also released in the extracellular compartment where it induces immune suppression. We investigated whether E7 was also responsible for the enhanced endothelial adhesiveness required in cancer progression. STUDY DESIGN/METHODS: We treated cervical microvascular endothelial cells (CrMVEn) and human umbilical vein endothelial cells (HUVEC) with E7, tumor necrosis factor-alpha (TNF-alpha), and hydrogen peroxide (H2O2) and measured the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by fluorescent-activated cell sorter analysis. RESULTS: E7 strongly induced the expression of E-selectin, ICAM-1, and VCAM-1 in CrMVEn, but not in HUVEC. Tumor necrosis factor-alpha further increased the endothelial expression of adhesion molecules in CrMVEn. Hydrogen peroxide pre-treatment resulted in an enhanced ICAM-1 and a decreased E-selectin and VCAM-1 expression. We also show indirect effects when endothelial cells were stimulated with the supernatant of E7-pretreated macrophages. CONCLUSIONS: These results show that HPV-16-E7 oncoprotein strongly induces adhesion molecules expression in organ-specific endothelial cells.

Cell Adhesion Molecules↗

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[Diagnostic problems in gastric dysplasias: value of cytology (author's transl)].

Gastric smears have been performed on 835 patients, among which examinations 771 (92 percent) were available. Histology assumed in parallel showed a dysplasia lesion in 56 cases: 14 of the 601 negative smears (2.3 percent), in 33 of the 40 suspect smears (82 percent), and in 9 of the 130 cases of positive smears (7 percent). Gastric dysplasia evidence both by cytology and pathology show mostly differenciated cells, alterations of which reflect the lesion level. By contrast, cytology and histology diagnosis are not in agreement when dysplasia concern dedifferenciated cells with a severe degree of alterations which can be misinterpreted as malignant cells.

Cytological Techniques↗

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[The current situation of research into a vaccine for AIDS].

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

[Randomization of a population for a clinical trial of immunization against the human immunodeficiency virus (HIV)].

Serum HIV antibodies has been investigated in different subpopulation from four different regions in Zäire by Elisa (Elavia Pasteur) and Western Blot. Seropositive prevalence differed from 2.4% (rural population) to 12.5% (urban population) according to the regions. When the group with 2.4% migrated to the area with 12.5% positives, after 8-12 months the number of seropositives in this group raised to 8%, showing an increase of 5.6% within one year. Such population is suitable for a large scale clinical trial (with anti-AIDS vaccine) to be performed on individuals with high risk of natural infection.

AIDS Serodiagnosis↗

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[Immunization against the human immunodeficiency virus in Zaire].

The first experimental immunization of human against the AIDS retrovirus HIV-1 was started in a series of HIV seronegative healthy volunteers in november 1986. Priming used a vaccinia virus recombinant (V25) expressing Gp 160 env determinants of HTLV III B at the surface of infected cells. This priming which induced a weak immune reaction was performed on HIV seronegative French and Zaïrian individuals living in Zaïre (Kinshasa). These results prompted to boost the primary immune response. Four different protocols were used: slow drip intravenous infusion with paraformaldehyde fixed autologous cells infected with V25 (first protocol), repeated scarification with V25 for the second protocol. The third protocol used scarifications with fragment of Gp 120 env protein, and the fourth protocol used intramuscular injections of purified autologous cell membrane infected with V25. Results of the immune reaction obtained after these boosts: The three last protocols showed a cell mediated immunity (CMI) that not significantly enhanced in comparison with CMI obtained after V25 priming alone. Moreover, the sera showed low and variable neutralizing antibodies titers one to four months after boosting. By contrast boosting with V25 infected fixed cells (D.Z. individual) provide strong humoral and cellular group specific anamnestic immune response. Indeed, high levels of antibodies to viral envelope and neutralizing antibodies against divergent HIV-1 strains were observed. Group specific CMI and cell mediated cytotoxicity were enhanced by boosts. Skin-tests showed high mediated and delayed hypersensitivity to GP 160 in vivo. For the first time, these results show that an immune stage against HIV can be obtained in a man.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Biology of isolated immunocytes. II. Simultaneous detection of cell surface Ig and theta-antigen by immunoperoxidase staining at the ultrastructural level.

Surface Ig and theta-antigen of lymphocytes collected on the bottom of Beem capsules were stained by an indirect immunoperoxidase technique to compare B and T cells at the ultrastructural level. To distinguish the two markers, the surface Ig was allowed to cap during the incubation with anti-Ig antiserum while the incubation with anti-theta alloantiserum was performed at 4 degrees to obtain a staining in a ring pattern. This method was applied to the study of lymphocytes from spleen, lymph nodes and thymus of normal mice. Lymphocytes forming rosettes with SRBC were also studied at different days after immunization with SRBC.

Animals↗