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Biomedical subjects

J R Savary

Publications and source records attributed to J R Savary.

6 recordsLinked to original sources
PubMed2000

Cell-mediated immune responses to autologous virus in HIV-1-seropositive individuals after treatment with an HIV-1 immunogen.

OBJECTIVE: We hypothesized that cell mediated immune responses to an HIV-1 immunogen (whole-killed, gp120-depleted HIV-1 in IFA, REMUNE) would include those to autologous virus. METHODS: Five chronically HIV-1 infected individuals were examined for HIV-specific immune responses to their own virus (autologous viral antigen) after treatment with an HIV-1 immunogen. RESULTS: Subjects had low proliferative responses to HIV and p24 antigens prior to immunization and mounted strong lymphocyte proliferative responses to the immunizing HIV-1 virus, native p24, and autologous viral antigen post immunization. Similarly, subjects produced low amounts of interferon-gamma in response to HIV and p24 antigens prior to immunization and increased their interferon-gamma production in response to HIV-1, native p24, and to autologous antigen post-immunization. Furthermore, beta-chemokine responses measured as migratory inhibitory protein-1beta production were low at baseline in response to HIV-1 and native p24 antigens and were enhanced post immunization to HIV-1, native p24, and autologous antigen. CONCLUSIONS: In this study HIV-specific immune responses to autologous virus were observed after treatment with an HIV-specific immunogen.

AIDS Vaccines↗
PubMed2000

HIV-1-Specific CD4 helper function in persons with chronic HIV-1 infection on antiviral drug therapy as measured by ELISPOT after treatment with an inactivated, gp120-depleted HIV-1 in incomplete Freund's adjuvant.

OBJECTIVE: We hypothesized that treatment of HIV-1-seropositive study subjects receiving potent antiviral therapy with an HIV-specific immune-based therapy would increase HIV-1-specific T-helper immune function. DESIGN: 10 HIV-1-seropositive study subjects receiving antiretroviral therapy were treated with an inactivated, gp120-depleted immunogen in IFA (HIV-1 immunogen, Remune) at baseline, week 12, and week 24. METHODS: The frequency of HIV-1 antigen-stimulated interferon-gamma (IFN-gamma)-producing cells was determined by the ELISPOT assay. RESULTS: Study subjects significantly increased their frequency of HIV-1-stimulated (p <. 001) or p24 antigen-stimulated (p <.01) IFN-gamma-producing cells after one, two, and three treatments of HIV-1 immunogen. Depletion of CD4 cells resulted in the strongest abrogation of the IFN-gamma response. The frequency of HIV-1 (r = 0.64; p =.0002) and p24 (r = 0. 72; p <.001) antigen-stimulated IFN-gamma-producing cells in the CD8-depleted population before and after treatment was associated with the lymphocyte-proliferative response. CONCLUSIONS: Treatment with HIV-1 immunogen significantly enhanced the frequency of HIV-1-specific IFN-gamma-producing cells. Studies are ongoing to determine the relationship between this reversal of HIV-specific anergy and virologic outcomes.

AIDS Vaccines↗
PubMed1998

A primer on HIV type 1-specific immune function and REMUNE.

The ability to recognize HIV antigens is lost early in HIV-1 infection. Individuals with nonprogressive HIV disease have been observed to mount strong immune responses against the virus and have become a paradigm to emulate with immune-based therapies. Highly active antiviral drug therapy (HAART) has now become the standard of care for HIV-1-infected individuals. Because HIV-specific anergy occurs early in HIV infection, HAART initiated after primary infection may not reconstitute HIV-specific immune function. We have been investigating the effects of an immune-based therapy, called REMUNE, in HIV-1-seropositive individuals. REMUNE has been observed to stimulate HIV-1-specific immune function measured by delayed-type hypersensitivity, lymphocyte proliferation, Th1 cytokine, and beta-chemokine production. Multiple Phase II studies and a Phase III clinical end-point study are ongoing in thousands of seropositive individuals in order to test the clinical utility of REMUNE. The clinical testing of REMUNE and other promising immune-based therapies may provide additional treatment modalities useful in the chronic management of HIV-1.

AIDS Vaccines↗
PubMed1987

Biological effects of short-term, high-concentration exposure to methyl isocyanate. VI. In vitro and in vivo complement activation studies.

The ability of MIC to induce complement activation in vitro and in vivo was investigated. For the in vitro studies, both human and guinea pig serum or EDTA-plasma samples were exposed to 1167 to 1260 ppm MIC vapor for 15 min at room temperature. The human serum samples exposed to MIC showed significant reductions in Factor B, C2, C4, C3, C5, and total hemolytic complement CH50 activity levels. C6 functional activity was unaffected. The C3, C5, and CH50 functional activities in guinea pig serum (the only functional tests conducted on these samples) were more sensitive to MIC-mediated reduction than the corresponding activity reductions observed in the human serum samples. The human and single guinea pig EDTA-plasma samples exposed to MIC vapor showed no evidence of C3 consumption but did show significant reductions in CH50 levels. Thus, MIC vapor was able to activate, and thereby reduce serum complement C3 activity in vitro by a complement-dependent process. However, the data suggest at least one complement component other than C3 was inactivated in EDTA-plasma by a complement-independent mechanism. For the in vivo studies, five pairs of guinea pigs were exposed to 644 to 702 ppm MIC vapor until one of the pair died (11-15 min). MIC exposure was then discontinued, the surviving guinea pig was sacrificed, and EDTA-plasma was obtained from both animals and analyzed for complement consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

CXCR4 and CCR5 expression on CD4+ T cells in vivo and HIV-1 antigen beta-chemokine production in vitro after treatment with HIV-1 immunogen (REMUNE).

BACKGROUND: The chemokine receptors CXCR4 and CCR5 have been identified as the major coreceptors for HIV-1 on CD4+ cells and macrophages. The natural ligands for these receptors are SDF-1 and the beta-chemokines (MIP-1alpha, MIP-1beta, RANTES), respectively, and are the products of a variety of immune cells, including CD8+ T lymphocytes. STUDY DESIGN/METHODS: We hypothesized that the ability to stimulate the natural ligands for these receptors using an immune based therapy might influence in vivo chemokine receptor expression. RESULTS: In vivo CXCR4 expression remained stable after treatment with an HIV-1 Immunogen (REMUNE), whereas CCR5 expression on CD4+ T cells decreased (p < .05). Furthermore, HIV-1 antigen-specific production of beta-chemokines in vitro was also augmented (P < .05). CONCLUSIONS: These preliminary results suggest that this HIV-1-specific immune-based therapy can stimulate antigen-specific beta-chemokine production in vitro and downregulate CCR5 receptor expression on CD4 cells in vivo.

AIDS Vaccines↗