Biomedical subjects

Anna Hryniewicz

Publications and source records attributed to Anna Hryniewicz.

6 recordsLinked to original sources

PubMed2006

Subunit recombinant vaccine protects against monkeypox.

The smallpox vaccine Dryvax, a live vaccinia virus (VACV), protects against smallpox and monkeypox, but is contraindicated in immunocompromised individuals. Because Abs to VACV mediate protection, a live virus vaccine could be substituted by a safe subunit protein-based vaccine able to induce a protective Ab response. We immunized rhesus macaques with plasmid DNA encoding the monkeypox orthologs of the VACV L1R, A27L, A33R, and B5R proteins by the intradermal and i.m. routes, either alone or in combination with the equivalent recombinant proteins produced in Escherichia coli. Animals that received only DNA failed to produce high titer Abs, developed innumerable skin lesions after challenge, and died in a manner similar to placebo controls. By contrast, the animals vaccinated with proteins developed moderate to severe disease (20-155 skin lesions) but survived. Importantly, those immunized with DNA and boosted with proteins had mild disease with 15 or fewer lesions that resolved within days. DNA/protein immunization elicited Th responses and binding Ab titers to all four proteins that correlated negatively with the total lesion number. The sera of the immunized macaques recognized a limited number of linear B cell epitopes that are highly conserved among orthopoxviruses. Their identification may guide future efforts to develop simpler, safer, and more effective vaccines for monkeypox and smallpox.

Amino Acid Sequence↗

PubMed2006

CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques.

Regulatory T (T(reg)) cells are a subset of CD25(+)CD4(+) T cells that constitutively express high levels of cytotoxic T lymphocyte antigen-4 (CTLA-4) and suppress T-cell activation and effector functions. T(reg) cells are increased in tissues of individuals infected with HIV-1 and macaques infected with simian immunodeficiency virus (SIV(mac251)). In HIV-1 infection, T(reg) cells could exert contrasting effects: they may limit viral replication by decreasing immune activation, or they may increase viral replication by suppressing virusspecific immune response. Thus, the outcome of blocking T(reg) function in HIV/SIV should be empirically tested. Here, we demonstrate that CD25(+) T cells inhibit virus-specific T-cell responses in cultured T cells from blood and lymph nodes of SIV-infected macaques. We investigated the impact of CTLA-4 blockade using the anti-CTLA-4 human antibody MDX-010 in SIV-infected macaques treated with antiretroviral therapy (ART). CTLA-4 blockade decreased expression of the tryptophan-depleting enzyme IDO and the level of the suppressive cytokine transforming growth factor-beta (TGF-beta) in tissues. CTLA-4 blockade was associated with decreased viral RNA levels in lymph nodes and an increase in the effector function of both SIV-specific CD4(+) and CD8(+) T cells. Therefore, blunting T(reg) function in macaques infected with SIV did not have detrimental virologic effects and may provide a valuable approach to complement ART and therapeutic vaccination in the treatment of HIV-1 infection.

AIDS Vaccines↗

PubMed2005

Contrasting effects of low-dose IL-2 on vaccine-boosted simian immunodeficiency virus (SIV)-specific CD4+ and CD8+ T cells in macaques chronically infected with SIVmac251.

IL-2, the first cytokine discovered with T cell growth factor activity, is now known to have pleiotropic effects on T cells. For example, it can promote growth, survival, and differentiation of Ag-selected cells, or facilitate Ag-induced cell death of T cells when Ag persists, and in vivo, it is thought to contribute to the regulation of the size of adaptive T cell response. IL-2 is deficient in HIV-1 infection and has been used in the management of HIV-1-infected individuals undergoing antiretroviral therapy. In this study, we investigated how continuous low-dose IL-2 affected the CD4+ and CD8+ T cell response induced by two inoculations of a canarypox recombinant SIV-based vaccine candidate in healthy macaques chronically infected with SIVmac251. These macaques had normal levels of CD4+ T cells at the beginning of antiretroviral therapy treatment. Vaccination in the presence of IL-2 significantly augmented Gag-specific CD8+ T cell responses, but actually reduced Gag-specific CD4+ T cell responses. Although IL-2 at low doses did not change the overall concentration of circulating CD4+ or CD8+ T cells, it expanded the frequency of CD4+CD25+ T cells. Depletion of the CD4+CD25+ T cells in vitro, however, did not result in a reconstitution of Gag-specific CD4+ responses or augmentation of SIV-specific CD8+ T cell responses. Thus, we conclude that the decrease in virus-specific CD4+ T cell response may be due to IL-2-promoted redistribution of cells from the circulation, or due to Ag-induced cell death, rather than suppression by a T regulatory population.

Adjuvants, Immunologic↗

PubMed2005

Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.

It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1)-infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG. Thus, vaccination strategies that bypass CD4(+) cell help are needed to elicit IgG antibodies with high affinity and adequate tissue distribution and to restore protection against smallpox in severely immunocompromised individuals.

Animals↗

PubMed2003

An immunohistochemical study of the thyroid parafollicular (C) cells in rats treated with cannabinoids - preliminary investigations.

The purpose of the present study was to evaluate the effect of a single intraperitoneal injection of a stable analogue of endogenous cannabinoid anandamide - R-(+)-methanandamide (2.5 mg/kg) and CP 55,940 (0.25 mg/kg), an egzogenous CB1 receptor-agonist, on the calcitonin (CT) immunoreactivity of the thyroid parafollicular (C) cells. Four hours after injection with both cannabinoids CT immunoreactivity, evaluated with an avidin-biotin peroxidase complex method by means of rabbit antibodies against CT, was seen to be enhanced in the parafollicular cells in comparison to those of the control group. In thyroids taken from cannabinoid-treated rats the majority of follicles, particularly those located peripherally were large in size, and had low epithelium. Moreover, dilatation of the blood vessels was observed. These changes were accompanied by a significant decrease in CT plasma level, without changes in calcium concentrations. This is the first evidence that a single injection of the cannabinoids R-(+)-methanandamide and CP 55,940 significantly decreases the activity of thyroid C cells.

Animals↗

PubMedDate not supplied

Cannabinoids alter recognition memory in rats.

Cannabinoids are known to attenuate learning and memory in both humans and animals. In rodents, disruptive effect of cannabinoids on memory, reversed by SR 141716, a specific CB(1) receptor antagonist, was shown in behavioral tests based on conditioning. There are no data concerning the influence of cannabinoids on recognition memory. Recently, the improvement of recognition memory in cannabinoid CB(1) receptor knock-out mice was reported. Therefore, the purpose of the present study was to determine whether a stable analogue of endogenous cannabinoid anandamide, R-(+)-methanandamide (0.25 and 2.5 mg/kg, i.p.) and a potent CB(1) receptor agonist, CP 55,940 (0.025 and 0.25 mg/kg i.p.) affect recognition memory in rats evaluated in an object recognition test, based on discrimination between the familiar and a new object presented at 1h interval. Because cannabinoids at the higher doses can produce motor inhibition, the influence of both compounds on psychomotor activity was evaluated in an open field test. CP 55,940 and R-(+)-methanandamide, at both doses given once, 15 min before the learning trial, significantly attenuated recognition memory, measured by the difference in exploration of a new object and a duplicate of the familiar object. Moreover, CP 55,940 at the higher dose significantly attenuated ambulation, and bar approaches, and at both doses also rearings, evaluated in an open field, performed immediately after an object recognition test, while R-(+)-methanandamide at both doses did not alter locomotor and exploratory activity of rats. This is the first evidence that cannabinoids impair recognition memory in rats.

Animals↗