Red blood cell-mediated delivery of recombinant HIV-1 Tat protein in mice induces anti-Tat neutralizing antibodies and CTL

Dominici, Sabrina; Laguardia, Maria Elena; Serafini, Giordano; Chiarantini, Laura; Fortini, Cinzia; Tripiciano, Antonella; Brocca-Cofano, Egidio; Scoglio, Arianna; Caputo, Antonella; Fiorelli, Valeria; Gavioli, Riccardo; Cafaro, Aurelio; Ensoli, Barbara; Magnani, Mauro

doi:10.1016/s0264-410x(02)00746-6

Cited by 43 publications

(26 citation statements)

References 64 publications

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“…Of these, biotinylation of TNF-α was proposed as an approach to direct the cytokine to the membrane of melanoma cells [17], and biotinylation of red blood cells as a potential antigen delivery system via the biotin-avidin-biotin bridge [18]. An interesting report demonstrates the safety and specificity of red blood cell delivery of HIV-Tat as a step in the design of a new anti-HIV vaccine [19]. To tweak our technique, we first performed biotin labeling of MSC membrane proteins with the biotinylating agent sulfo-NHS-biotin reagents (Fig.…”

Section: Discussionmentioning

confidence: 99%

Homing of annexin-labeled stem cells to apoptotic cells

Gerasimou¹,

Ramella²,

Brero³

et al. 2009

Cellular and Molecular Biology Letters

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Ischemic diseases are characterized by the presence of pro-apoptotic stimuli, which initiate a cascade of processes that lead to cell injury and death. Several molecules and events represent detectable indicators of the different stages of apoptosis. Among these indicators is phosphatidylserine (PS) translocation from the inner to the outer leaflet of the plasma membrane, which can be detected by annexinV (ANXA5) conjugation. This is a widely used in vivo and in vitro assay marking the early stages of apoptosis. We report here on an original method that employs PS-ANXA5 conjugation to target stem cells to apoptotic cells. Mesenchymal stem cells (MSCs) from GFP-positive transgenic rats were biotinylated on membrane surfaces with sulfosuccinimidyl-6-(biotinamido) hexanoate (sulfo-NHS-LC-biot) and then bound to avidin. The avidin-biotinylated MSCs were labeled with biotin conjugated ANXA5. Bovine aortic endothelial cells (BAE-1 cells) were exposed to UVC to induce caspasedependent apoptosis. Finally, we tested the ability of ANXA5-labeled MSCs to Unauthenticated Download Date | 5/11/18 2:02 AM CELLULAR & MOLECULAR BIOLOGY LETTERS 101 bind BAE-1 apoptotic cells: suspended ANXA5-labeled MSCs were seeded for 1 hour on a monolayer of UV-treated or control BAE-1 cells. After washing, the number of MSCs bound to BAE-1 cells was evaluated by confocal microscopy. Statistical analysis demonstrated a significant increase in the number of MSCs tagged to apoptotic BAE-1 cells. Therefore, stem cell ANXA5 tagging via biotin-avidin bridges could be a straightforward method of improving homing to apoptotic tissues.

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Section: Discussionmentioning

confidence: 99%

Homing of annexin-labeled stem cells to apoptotic cells

Gerasimou¹,

Ramella²,

Brero³

et al. 2009

Cellular and Molecular Biology Letters

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“…Nevertheless, due to the possible side effects of Tat (14,53,69,70,72), administration of active Tat to patients might pose serious safety concerns. Chemically modified Tat-based vaccines have been proposed as an attractive option (18,52,67). However, immunization of macaques with Tat toxoid concomitantly with an adjuvant only attenuated disease (52).…”

Section: Discussionmentioning

confidence: 99%

Induction of Neutralizing Antibodies and Th1-Polarized and CD4-Independent CD8⁺T-Cell Responses following Delivery of Human Immunodeficiency Virus Type 1 Tat Protein by Recombinant Adenylate Cyclase ofBordetella pertussis

Mascarell

Fayolle

Bauche

et al. 2005

J Virol

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HIV-Tat, a conserved protein playing a key role in the early life cycle of the human immunodeficiency virus (HIV) has been proposed as a potential AIDS vaccine. An HIV-Tat-based vaccine should elicit a broad, long-lasting, and neutralizing immune response. We have previously demonstrated that the adenylate cyclase (CyaA) from Bordetella pertussis targets dendritic cells and delivers CD8؉ and CD4 ؉ T-cell epitopes into the major histocompatibility complex class I and class II presentation pathways. We have also showed that CyaA induced specific and protective cytotoxic T cell responses in vivo. Here, we designed a prototype vaccine based on the HIV type 1 Tat delivered by CyaA (CyaA-E5-Tat) and tested its capacity to induce HIV-Tat-specific cellular as well as antibody responses. We showed that immunization of mice by CyaA-E5-Tat in the absence of adjuvant elicited strong and long-lasting neutralizing anti-Tat antibody responses more efficient than those obtained after immunization with Tat toxoid in aluminum hydroxide adjuvant. Analyses of the anti-Tat immunoglobulin G isotypes and the cytokine pattern showed that CyaA-E5-Tat induced a Th1-polarized immune response in contrast to the Th2-polarized immune responses obtained with the Tat toxoid. In addition, our data demonstrated that HIV-Tat-specific gamma interferon-producing CD8 ؉ T cells were generated after vaccination with CyaA-E5-Tat in a CD4؉ T-cell-independent manner. Based on these findings, CyaA-E5-Tat represents an attractive vaccine candidate for both preventive and therapeutic vaccination involving CyaA as an efficient nonreplicative vector for protein delivery.

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“…We have examined the ability of three Aβ-degrading enzymes, neprilysin (NEP) [16], insulysin (IDE) [36], and metalloprotease-1 (MP-1) [12] coupled to erythrocytes to degrade Aβ both in vitro and in vivo. Expression of Aβ-degrading enzymes in the periphery represents a novel way to lower plasma Aβlevels by hydrolytic cleavage rather than by forming Aβ complexes, and the use of erythrocyte coupling as a drug delivery system has been shown to be a promising therapeutic avenue [9,26,33]. Although brain expression of Aβ-degrading enzymes as a way to lower brain Aβ levels has been used successfully in a number of studies [15,18,22,29] peripheral expression has not been explored to any great extent.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo degradation of Aβ peptide by peptidases coupled to erythrocytes

et al. 2007

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It is generally believed that amyloid β peptides (Aβ) are the key mediators of Alzheimer's disease. Therapeutic interventions have been directed toward impairing the synthesis or accelerating the clearance of Aβ. An equilibrium between blood and brain Aβ exists mediated by carriers that transport Aβ across the blood brain barrier. Passive immunotherapy has been shown to be effective in mouse models of AD, where the plasma borne antibody binds plasma Aβ causing an efflux of Aβ from the brain. As an alternative to passive immunotherapy we have considered the use of Aβ-degrading peptidases to lower plasma Aβ levels. Here we compare the ability of three Aβ-degrading peptidases Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Red blood cell-mediated delivery of recombinant HIV-1 Tat protein in mice induces anti-Tat neutralizing antibodies and CTL

Cited by 43 publications

References 64 publications

Homing of annexin-labeled stem cells to apoptotic cells

Homing of annexin-labeled stem cells to apoptotic cells

Induction of Neutralizing Antibodies and Th1-Polarized and CD4-Independent CD8⁺T-Cell Responses following Delivery of Human Immunodeficiency Virus Type 1 Tat Protein by Recombinant Adenylate Cyclase ofBordetella pertussis

In vitro and in vivo degradation of Aβ peptide by peptidases coupled to erythrocytes

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Red blood cell-mediated delivery of recombinant HIV-1 Tat protein in mice induces anti-Tat neutralizing antibodies and CTL

Cited by 43 publications

References 64 publications

Homing of annexin-labeled stem cells to apoptotic cells

Homing of annexin-labeled stem cells to apoptotic cells

Induction of Neutralizing Antibodies and Th1-Polarized and CD4-Independent CD8+T-Cell Responses following Delivery of Human Immunodeficiency Virus Type 1 Tat Protein by Recombinant Adenylate Cyclase ofBordetella pertussis

In vitro and in vivo degradation of Aβ peptide by peptidases coupled to erythrocytes

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Induction of Neutralizing Antibodies and Th1-Polarized and CD4-Independent CD8⁺T-Cell Responses following Delivery of Human Immunodeficiency Virus Type 1 Tat Protein by Recombinant Adenylate Cyclase ofBordetella pertussis