Therapeutic immunization in HIV infection

Autran, Brigitte; Loés, Sabine Kinloch-de; Katlama, Christine

doi:10.1097/01.coh.0000232348.15909.c6

Cited by 5 publications

(4 citation statements)

References 73 publications

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“…Nevertheless, the tentative correlates of protection described above justified using T-cell-based vaccines (6,12,93,107,108). Nevertheless, the tentative correlates of protection described above justified using T-cell-based vaccines (6,12,93,107,108).…”

Section: Results From Therapeutic Vaccine Trials Against Hivmentioning

confidence: 99%

“…Therapeutic immunization strategies were launched at a time when no effective preventative vaccine was yet available. Nevertheless, the tentative correlates of protection described above justified using T-cell-based vaccines (6,12,93,107,108). Although the passive administrations of neutralizing antibodies had shown some efficacy at controlling HIV during STIs (109), the high antibody concentrations required to control the virus and the lack of appropriate immunogens capable to induce such antibodies led to abandoning antibody-based strategies.…”

Section: Results From Therapeutic Vaccine Trials Against Hivmentioning

confidence: 99%

“…Re-immunizing HIV-infected patients against HIV first required cART to reverse the immunopathological consequences of HIV replication and variability, to restore effective immune competence, then to add therapeutic vaccines to boost the rested immune responses to HIV before interrupting treatment (6,12,93,107,108). The hypothesis was that such a synergistic combination of cART plus vaccines would provide optimal and durable vaccine-induced HIV-1 specific T-cell responses to control HIV when cART is discontinued, before the virus reaches overwhelming levels.…”

Section: Challenges Opposed To Therapeutic Immunization Against Hiv Amentioning

confidence: 99%

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Immune interventions in HIV infection

Carcelain

Autran

2013

Immunological Reviews

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Immune-based therapy (IBT) interventions have found a window of opportunity within some limitations of the otherwise successful combined antiretroviral therapy (cART). Two major paradigms drove immunotherapeutic research to combat human immunodeficiency virus (HIV) infection. First, IBTs were proposed either to help restore CD4(+) T-cell counts in cases of therapeutic failures with cytokines, interleukin-2 (IL-2) or IL-7, or to better control HIV and disease progression during treatment interruptions with anti-HIV therapeutic candidate vaccines. The most widely used candidates were HIV-recombinant live vector-based alone or combined with other vaccine compounds and dendritic cell (DC) therapies. A more recent and current paradigm aims at achieving HIV cure by combining IBT with cART using either cytokines to reactivate virus production in latently infected cells and/or therapeutic immunization to boost HIV-specific immunity in a 'shock and kill' strategy. This review summarizes the rationale, hopes, and mechanisms of successes and failures of these cytokine-based and vaccine-based immune interventions. Results from these first series of IBTs have been so far somewhat disappointing in terms of clinical relevance, but have provided lessons that are discussed in light of the future combined strategies to be developed toward an HIV cure.

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Section: Results From Therapeutic Vaccine Trials Against Hivmentioning

confidence: 99%

Section: Results From Therapeutic Vaccine Trials Against Hivmentioning

confidence: 99%

Section: Challenges Opposed To Therapeutic Immunization Against Hiv Amentioning

confidence: 99%

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Immune interventions in HIV infection

Carcelain

Autran

2013

Immunological Reviews

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“…Treatment intensification with additional or more potent cART, cytokine therapy and therapeutic vaccination has not had a clinically meaningful impact up to the present [15–19]. Age, especially over 40–45 years old, and lower naïve CD4 + T-cells prior to initiating cART, are the most reliable baseline characteristic associated with blunted CD4 + T-cell rise [20, 21].…”

Section: Introductionmentioning

confidence: 99%

Role of intestinal myofibroblasts in HIV-associated intestinal collagen deposition and immune reconstitution following combination antiretroviral therapy

Asmuth

Pinchuk

et al. 2015

Aids

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Objective To investigate the potential role of mucosal intestinal myofibroblasts (IMFs) in HIV and associated fibrosis in GALT. Design Profibrotic changes within the secondary lymphoid organs and mucosa has been implicated in failed immune reconstitution following effective cART. Microbial translocation is believed to be sustaining these systemic inflammatory pathways. IMFs are non-professional antigen-presenting cells with both immunoregulatory and mesenchymal functions that are ideally positioned to respond to translocating microbial antigen. Methods Duodenal biopsies obtained from patients naïve to cART underwent trichrome staining and examined for TGF-β expression. Combined immunostaining and second harmonic generation-analysis was used to determine IMF activation and collagen deposition. Confocal microscopy was performed to examine for IMF activation and TLR4 expression. Finally, primary IMF cultures were stimulated with LPS to demonstrate expression of inflammatory biomarkers. Results The expression of the fibrosis-promoting molecule, TGF-β1, is significantly increased in duodenal biopsies from HIV patients naïve to cART and negatively correlated with subsequent peripheral CD4 recovery. The TGFβ1 increases coincided with an increase in collagen deposition in duodenal mucosa in tissue area adjacent to IMFs. We also observed that IMFs expressed TLR4 and had an activated phenotype since they were positive for fibroblast activation protein. Finally, stimulation of IMFs from HIV patients with TLR4 resulted in significantly increased expression of profibrotic molecules, TGF-β1 and IL-6. Conclusions Our data support the hypothesis that activated IMFs may be among the major cells contributing to the profibrotic changes and thus, the establishment and maintenance of systemic inflammation interfering with immune reconstitution in HIV patients.

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