Biomedical subjects

Anne-Marte Bakken Kran

Publications and source records attributed to Anne-Marte Bakken Kran.

4 recordsLinked to original sources

PubMed2006

[Immunopathogenesis and therapeutic immunization in HIV-infection].

BACKGROUND: Modern antiretroviral treatment has improved the prognosis in chronic HIV-infection dramatically during the last decade; but the treatment is expensive, the drugs are toxic, and viral resistance is a problem. An alternative approach is therapeutic immunization. This treatment aims to improve the patients' own HIV-specific immune responses and thereby control the HIV-infection and suppress disease progression. MATERIAL AND METHODS: The article reviews therapeutic immunization in chronic HIV-infection, provides a brief overview of the immunopathogenesis of AIDS, and is partly based on studies performed at Ullevål University Hospital. RESULTS AND INTERPRETATION: Although different strategies for immune modulation in HIV-infection have shown to induce good, HIV-specific immune responses, there has been no definite documentation of clinical benefit so far. The most promising results have been obtained by immunizing patients with injections of virus-stimulated autologous dendritic cells, demonstrating a significant reduction of the viral load. The method is complex and therefore only feasible for individualised therapy in highly specialized clinics. At Ullevål University Hospital, we have in collaboration with Bionor Immuno recently conducted studies with a therapeutic immunization candidate Vacc-4x. Vacc-4x improves HIV-specific immune responses by stimulating skin dendritic cells with HIV-like peptides. Provision of efficient therapeutic immunization methods in chronic HIV-infection seems to be more realistic now than a few years ago. These methods may postpone and even reduce the need for antiretroviral treatment, and might also be beneficial if used as prophylactic immunization.

AIDS Vaccines↗

PubMed2006

Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment.

OBJECTIVES: To examine the immune modulating effects of cyclooxygenase type 2 (COX-2) inhibitors (COX-2i) in HIV-infected patients on combination antiretroviral treatment (CART). DESIGN: In-depth substudy from an approved, open, controlled, randomized study comparing the immune modulating effects of CART in combination with COX-2i after 12 weeks. METHODS: Patients (n = 38) on long-term CART with stable viral load (VL) < 50,000 copies/ml and CD4+ T-cell counts > 100/microl were randomized to CART and rofecoxib 25 mg bid (n = 12) or celecoxib 400 mg bid (n = 12), or CART only without placebo (n = 14). Routine clinical chemistry, CD4+ and CD8+ counts and VL were safety parameters. Immunological parameters included C-reactive protein, beta2-microglobulin, Ig isotypes and IgG subclasses as well as several T-lymphocyte subsets. Non-parametric analyses were used throughout. RESULTS: Prestudy experiments showed higher median intracellular expression of COX-2 in CD4+ (P = 0.048) and possibly CD8+ (P = 0.09) T cells from patients on CART compared with uninfected controls. In the clinical study, increased CD4+ T-cell counts were observed only in patients on COX-2i with VL < 50 copies/ml (P = 0.02). Decreased expression of CD38+ on CD8+ T cells and subsets as well as reductions in IgA and IgM (P < 0.03) were most pronounced in patients on COX-2i who had detectable VL (n = 6). COX-2i treatment enhanced the perforin content particularly in the differentiated CD27-/CD8+ T-cell subsets compared with controls (P = 0.05). CONCLUSIONS: COX-2i together with CART improved markers for persistent immune activation, particularly in patients with viraemia, as well as enhanced perforin expression, and thereby strengthened COX-2 as a potential therapeutic target in HIV infection.

ADP-ribosyl Cyclase 1↗

PubMed2005

Multiple antigen concentrations in delayed-type hypersensitivity (DTH) and response diversity during and after immunization with a peptide-based HIV-1 immunotherapy candidate (Vacc-4x).

Delayed-type hypersensitivity (DTH) testing represents a simple in vivo method for monitoring cellular immune responses. In a phase II clinical trial on HIV-infected patients (n = 38) of the peptide-based HIV-1 immunotherapy candidate Vacc-4x, we monitored DTH responses to three antigen concentrations of Vacc-4x. We have shown that DTH can be used quantitatively to measure immune reactions to Vacc-4x and its individual peptide components. Our data stress the qualities and differences of induration and erythema, both in discriminating individual antigens and in monitoring immunizations over time. The data also indicate that DTH baseline-status might have important impact on immunization kinetics.

AIDS Vaccines↗

PubMed2005

Divergent in vitro and in vivo correlates of HIV-specific T-cell responses during onset of HIV viraemia.

BACKGROUND: Cellular immune responses to HIV-1 have been examined mainly in peripheral blood mononuclear cells (PBMC). During onset of HIV replication and antigenaemia after discontinuation of highly active antiretroviral therapy (HAART), PBMC may theoretically contain HIV-specific T cells that are qualitatively and quantitatively different from specific T cells dominating in the tissues. PBMC responses throughout HIV immunotherapy trials may therefore be skewed during recurrent viraemia. OBJECTIVE: To compare cellular HIV-specific in vitro responses in PBMC during onset of HIV viraemia with corresponding in vivo responses, represented by classical delayed-type hypersensitivity tests (DTH). METHODS: HIV patients (n = 38), pre-immunized with four HIV-1 p24-like consensus peptides (Vacc-4x) during HAART, were subjected to a 14-week treatment interruption with recurrent HIV viraemia. Proliferative T-cell responses to Vacc-4x p24 peptides, HIV p24 protein, and cytomegalovirus (CMV) proteins were measured in PBMC. Corresponding Vacc-4x peptide DTH were expressed as skin infiltrate areas after 48 h. RESULTS: After 14 weeks without HAART, HIV-1 RNA increased to 72,500 copies/ml (median). The Vacc-4x p24 peptide- and HIV-1 p24 protein-induced T-cell proliferation concurrently decreased by 81 and 93% in PBMC during viraemia (medians, P < or = 0.03), whereas proliferative responses to CMV antigens were stable. In contrast, the Vacc-4x DTH areas, rather tended to increase by 36% (P = 0.08) and contained infiltrates dominated by proliferating T cells and macrophages. CONCLUSIONS: Divergent in vitro and in vivo HIV-specific cellular immune responses were found during recurrent HIV viraemia. The clinical relevance of both surrogate markers for HIV-related immune responses should be compared in future studies.

AIDS Vaccines↗