The Experts below are selected from a list of 12864 Experts worldwide ranked by ideXlab platform

Ann Depicker - One of the best experts on this subject based on the ideXlab platform.

  • simplified monomeric vhh fc antibodies provide new opportunities for Passive Immunization
    Current Opinion in Biotechnology, 2020
    Co-Authors: Henri De Greve, Vikram Virdi, Shruti Bakshi, Ann Depicker
    Abstract:

    Simplified monomeric monoclonal antibodies consisting of a single-domain VHH, derived from camelid heavy-chain only antibodies, fused with the Fc domain of either IgG (VHH-IgG) or IgA (VHH-IgA) antibodies, are promising therapeutic proteins. These simplified single-gene encoded antibodies are much easier to manufacture and can be produced in plants and in yeast for bulk applications. These merits enable novel Passive Immunization applications, such as in-feed oral delivery of VHH-IgAs, which have successfully provided protection against a gastrointestinal infection in the piglet model.

  • recombinant iga production for mucosal Passive Immunization advancing beyond the hurdles
    Cellular and Molecular Life Sciences, 2016
    Co-Authors: Vikram Virdi, Paloma Juarez, Veronique Boudolf, Ann Depicker
    Abstract:

    Vaccination is a successful strategy to proactively develop immunity to a certain pathogen, but most vaccines fail to trigger a specific immune response at the mucosal surfaces, which are the first port of entry for infectious agents. At the mucosal surfaces, the predominant immunoglobulin is secretory IgA (SIgA) that specifically neutralizes viruses and prevents bacterial colonization. Mucosal Passive Immunization, i.e. the application of pathogen-specific SIgAs at the mucosae, can be an effective alternative to achieve mucosal protection. However, this approach is not straightforward, mainly because SIgAs are difficult to obtain from convalescent sources, while recombinant SIgA production is challenging due to its complex structure. This review provides an overview of manufacturing difficulties presented by the unique structural diversity of SIgAs, and the innovative solutions being explored for SIgA production in mammalian and plant expression systems.

  • Role of plant expression systems in antibody production for Passive Immunization
    International Journal of Developmental Biology, 2013
    Co-Authors: Vikram Virdi, Ann Depicker
    Abstract:

    Passive Immunization is a method to achieve immediate protection against infectious agents by administering pathogen-specific antibodies. It has proven to be lifesaving for many acute infections, and it is now also used for cancer treatment. Passive Immunization therapies, however, are extremely expensive because they require large amounts of specific antibodies that are produced predominantly in mammalian expression systems. The cost for manufacturing plant-made antibodies is estimated to be comparatively low since plant production systems require relatively less capital investments. In addition, they are not prone to mammalian pathogens, which also eases downstream processing along with making it a safe expression system. Moreover, some of the recent developments in transient expression have enabled rapid, cGMP (current Good Manufacturing Practices) compliant manufacturing of antibodies. Whether lower production costs will be reflected in a lower market price for purified antibodies will be known when more plant-produced antibodies come to the market. Promisingly, the current mo-lecular techniques in the field of in planta expression have enabled high-level production of a variety of antibodies in different plant organs, like roots/tubers/fruits, leaves and seeds, of a va-riety of plants, like potato, tobacco, maize, rice, tomato and pea, providing a very wide range of possible plant-based Passive Immunization therapies. For instance, the production of antibodies in edible tissues would allow for a unique, convenient, needle-less, oral Passive Immunization at the gastric mucosal surface. The technological advances, together with the innate capacity of plant tissues to assemble complex antibodies, will enable carving a niche in the antibody market. This non-exhaustive review aims to shed light on the role of plants as a flexible expression system for Passive immunotherapy, which we envisage to progress alongside the conventional production platforms to manufacture specialized antibodies.

Neelima B. Chauhan - One of the best experts on this subject based on the ideXlab platform.

  • Intracerebroventricular Passive Immunization with anti-oligoAβ antibody in TgCRND8
    Journal of neuroscience research, 2007
    Co-Authors: Neelima B. Chauhan
    Abstract:

    Based on the central dogma of beta-amyloid (Abeta) as a key seeding event in the pathogenesis of Alzheimer disease (AD), immunoneutralization strategies have been actively pursued both in AD and in models of AD as a potential means for treating AD. Both active and Passive Immunizations targeted at fibrillar Abeta successfully remove cerebral plaque load and attenuate Abeta-induced toxicity. Consistently with this, intracerebroventricular (ICV) Passive Immunization established in our laboratory using antibody against fibrillar Abeta (anti-fAbeta) reduced cerebral plaque load and reversed early synaptic deficits at pre/early plaque stage when there is an abundance of soluble dimeric/oligomeric Abeta but sparse fibrillar Abeta, indicating that anti-fAbeta-mediated partial neutralization of toxic oligomeric Abeta species might have reduced early synaptotoxicity. In the previous investigation, we found that immunoneutralization with anti-fAbeta transiently reduced cerebral Abeta and associated toxicity. The current investigation tested whether ICV im munization using antibody to conformationally changed oligomeric Abeta (anti-oligoAbeta) will overcome the transient restorative nature of anti-fAbeta and produce persistent, long-lasting preventive effects. Because oligomeric Abeta is strongly correlated with synaptotoxicity, we investigated whether immunoneutralization of oligomeric Abeta will reverse synaptic deficits by analyzing presynaptic molecular marker (SNAP-25) profile within hippocampal dendritic fields, where SNAP-25 is abundantly expressed. Results show that, in contrast to ICV anti-fAbeta antibody, ICV anti-oligoAbeta antibody significantly prevented cerebral Abeta build and almost completely restored SNAP-25 immunoreaction up to 8 weeks postinjection in TgCRND8 brain. Results show that ICV Passive Immunization with anti-oligoAbeta antibody might be an improved ICV Immunization strategy for preventing permanent structural damage in AD.

  • Intracerebroventricular Passive Immunization in transgenic mouse models of Alzheimer's disease.
    Expert Review of Vaccines, 2004
    Co-Authors: Neelima B. Chauhan, George J. Siegel
    Abstract:

    Since uncontrolled production of β-amyloid (Aβ) is considered a key seeding event underlying progression of Alzheimer’s disease (AD), elimination of excessive Aβ and preventing its reaccumulation constitute the primary therapeutic goal in preventing and treating AD. To date, immunoneutralization has been the most effective strategy in removing pre-existing cerebral Aβ. Both active and systemic Passive Immunizations are known to reduce cerebral Aβ and improve memory in transgenic murine models of AD. However, active Immunization is associated with adverse effects such as encephalitis with perivascular inflammation and hemorrhage, while Passive Immunization has the potential to disrupt cerebral vasculature that is laden with amyloid and exposed to high levels of antibody in the blood. Intriguingly, intracerebroventricular Passive Immunization established in the authors’ laboratory circumvented these problems. The authors demonstrated that a single intracerebroventricular injection of anti-Aβ antibody reduce...

  • Intracerebroventricular Passive Immunization in transgenic mouse models of Alzheimer's disease.
    Expert review of vaccines, 2004
    Co-Authors: Neelima B. Chauhan, George J. Siegel
    Abstract:

    Since uncontrolled production of beta-amyloid (Abeta) is considered a key seeding event underlying progression of Alzheimer's disease (AD), elimination of excessive Abeta and preventing its reaccumulation constitute the primary therapeutic goal in preventing and treating AD. To date, immunoneutralization has been the most effective strategy in removing pre-existing cerebral Abeta. Both active and systemic Passive Immunizations are known to reduce cerebral Abeta and improve memory in transgenic murine models of AD. However, active Immunization is associated with adverse effects such as encephalitis with perivascular inflammation and hemorrhage, while Passive Immunization has the potential to disrupt cerebral vasculature that is laden with amyloid and exposed to high levels of antibody in the blood. Intriguingly, intracerebroventricular Passive Immunization established in the authors' laboratory circumvented these problems. The authors demonstrated that a single intracerebroventricular injection of anti-Abeta antibody reduced the cerebral Abeta burden and Abeta-related astrocytosis, retarded reaccumulation of Abeta and restored Abeta-induced depletion of presynaptic SNAP-25, for at least 1 month and reduced inflammatory reactions for 1 week in AD murine models without producing inflammation, microhemorrhage or systemic histotoxicity. These facts suggest that intracerebroventricular anti-Abeta may be a safe method for the rapid clearance of pre-existing Abeta and retarding reaccumulation of Abeta in AD. Intracerebroventricular administration via a catheter and reservoir, may be combined with the development of humanized monoclonal antibody against Abeta. Intraventricular shunts and ventriculostomy are frequently employed with acceptable risk-to-benefit ratios in the treatment of various brain disorders, while humanized antibodies are currently used in clinical trials of brain diseases such as multiple sclerosis and lymphoma.

George J. Siegel - One of the best experts on this subject based on the ideXlab platform.

  • Intracerebroventricular Passive Immunization in transgenic mouse models of Alzheimer's disease.
    Expert Review of Vaccines, 2004
    Co-Authors: Neelima B. Chauhan, George J. Siegel
    Abstract:

    Since uncontrolled production of β-amyloid (Aβ) is considered a key seeding event underlying progression of Alzheimer’s disease (AD), elimination of excessive Aβ and preventing its reaccumulation constitute the primary therapeutic goal in preventing and treating AD. To date, immunoneutralization has been the most effective strategy in removing pre-existing cerebral Aβ. Both active and systemic Passive Immunizations are known to reduce cerebral Aβ and improve memory in transgenic murine models of AD. However, active Immunization is associated with adverse effects such as encephalitis with perivascular inflammation and hemorrhage, while Passive Immunization has the potential to disrupt cerebral vasculature that is laden with amyloid and exposed to high levels of antibody in the blood. Intriguingly, intracerebroventricular Passive Immunization established in the authors’ laboratory circumvented these problems. The authors demonstrated that a single intracerebroventricular injection of anti-Aβ antibody reduce...

  • Intracerebroventricular Passive Immunization in transgenic mouse models of Alzheimer's disease.
    Expert review of vaccines, 2004
    Co-Authors: Neelima B. Chauhan, George J. Siegel
    Abstract:

    Since uncontrolled production of beta-amyloid (Abeta) is considered a key seeding event underlying progression of Alzheimer's disease (AD), elimination of excessive Abeta and preventing its reaccumulation constitute the primary therapeutic goal in preventing and treating AD. To date, immunoneutralization has been the most effective strategy in removing pre-existing cerebral Abeta. Both active and systemic Passive Immunizations are known to reduce cerebral Abeta and improve memory in transgenic murine models of AD. However, active Immunization is associated with adverse effects such as encephalitis with perivascular inflammation and hemorrhage, while Passive Immunization has the potential to disrupt cerebral vasculature that is laden with amyloid and exposed to high levels of antibody in the blood. Intriguingly, intracerebroventricular Passive Immunization established in the authors' laboratory circumvented these problems. The authors demonstrated that a single intracerebroventricular injection of anti-Abeta antibody reduced the cerebral Abeta burden and Abeta-related astrocytosis, retarded reaccumulation of Abeta and restored Abeta-induced depletion of presynaptic SNAP-25, for at least 1 month and reduced inflammatory reactions for 1 week in AD murine models without producing inflammation, microhemorrhage or systemic histotoxicity. These facts suggest that intracerebroventricular anti-Abeta may be a safe method for the rapid clearance of pre-existing Abeta and retarding reaccumulation of Abeta in AD. Intracerebroventricular administration via a catheter and reservoir, may be combined with the development of humanized monoclonal antibody against Abeta. Intraventricular shunts and ventriculostomy are frequently employed with acceptable risk-to-benefit ratios in the treatment of various brain disorders, while humanized antibodies are currently used in clinical trials of brain diseases such as multiple sclerosis and lymphoma.

Ruth M. Ruprecht - One of the best experts on this subject based on the ideXlab platform.

  • Anti-HIV Passive Immunization: New Weapons in the Arsenal.
    Trends in microbiology, 2017
    Co-Authors: Ruth M. Ruprecht
    Abstract:

    Anti-HIV Passive Immunization with human neutralizing monoclonal antibodies (nmAbs) has made exciting gains: (i) identification of the HIV envelope V2 apex as a new in vivo protective epitope, (ii) a novel clade C SHIV for challenge studies, and (iii) a highly protective, trispecific nmAb. Potent, broad-spectrum protection by nmAbs holds promise.

  • Passive Immunization with human neutralizing monoclonal antibodies against hiv 1 in macaque models experimental approaches
    Methods of Molecular Biology, 2009
    Co-Authors: Ruth M. Ruprecht
    Abstract:

    After more than 20 years of intense research, a safe and effective vaccine against HIV-1/AIDS has not been developed. Passive Immunization has been used as a tool to demonstrate the role of neutralizing antibodies in conferring protection against HIV-1 challenge in chimpanzees. Because these animals are endangered and studies are difficult to conduct with this species, chimeric viruses, termed simian-human immunodeficiency viruses (SHIVs), have been generated that encode the HIV-1 envelope gene in the backbone of the simian immunodeficiency virus (SIV). SHIVs replicate in several macaque species and can induce AIDS in these animals. Passive Immunization with human neutralizing monoclonal antibodies (nmAbs) against HIV-1 has protected rhesus macaques from SHIV infection and provided proof-of-concept of the protective effects of neutralizing antibodies. At the same time, human nmAbs can be evaluated for safety and efficacy in the SHIV/macaque model as therapeutic modalities in their own right for prevention, post-exposure prophylaxis, or possibly therapeutic use. Experimental details are provided for testing human nmAbs in infant rhesus monkeys, which allows testing without the need to generate large amounts of nmAbs.

  • Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes
    Current HIV research, 2007
    Co-Authors: Victor G. Kramer, Nagadenahalli B. Siddappa, Ruth M. Ruprecht
    Abstract:

    The HIV-1/AIDS epidemic continues to escalate, and a protective vaccine remains elusive. The first vaccine candidate, gp120, did not induce broadly neutralizing antibodies (nAbs) against primary HIV-1 isolates and was ineffective in phase III clinical trials. Attention then focused on generating cytotoxic lymphocyte (CTL)-based vaccines. Interest in anti-HIV-1 nAbs was renewed when Passive Immunization with human neutralizing monoclonal antibodies (nmAbs) completely protected macaques after intravenous and mucosal challenges with simian-human immunodeficiency viruses (SHIVs) encoding HIV-1 env. These nmAbs targeted conserved, functionally important epitopes on gp120 and gp41. Protection in primate/SHIV models was observed when nmAbs were used singly (nmAbs 2G12, b12) and in various combination regimens (nmAbs b12, F105, 2G12, 2F5, 4E10). Passive Immunization, a well-established tool to determine the correlates of protective immunity, thus identified protective epitopes. The three-dimensional structures of some of the latter were recently elucidated, generating important information to design nAb-response-base immunogens. However, several of the protective nmAbs were found to exhibit autoreactivity, raising the possibility that B-cell responses against the cognate epitopes may be difficult to induce by active Immunization. It will be important to explore whether broad neutralization can be dissociated from autoreactivity. Future experiments will reveal whether other conserved HIV-1 Env epitopes exist, antibodies against which will be broadly neutralizing in vitro, protective as Passive Immunization in SHIVchallenged macaques, but lacking autoreactivity. Since all protective epitopes identified to date are located on HIV-1 clade B Env, future studies should include analysis of nmAbs against non-clade B strains.

  • Antibody protection: Passive Immunization of neonates against oral AIDS virus challenge.
    Vaccine, 2003
    Co-Authors: Ruth M. Ruprecht, Flavia Ferrantelli, Moiz Kitabwalla, Harold M. Mcclure
    Abstract:

    Abstract We have established models for intrapartum and milk-borne HIV transmission by orally challenging neonatal macaques with chimeric simian–human immunodeficiency viruses (SHIVs). This allowed us to test safety and efficacy of Passive Immunization with human neutralizing monoclonal antibodies (nmAbs), which had been isolated from HIV clade B-infected individuals and which target conserved, functionally important epitopes. The nmAbs studied were F105 or IgG1b12, b12 for short (directed against the CD4 binding site), 2G12 (anti-gp120), 2F5 and 4E10 (both anti-gp41). Out of 16 newborn macaques challenged orally with different SHIV strains, 11 were completely protected by triple or quadruple nmAb combinations, even by post-exposure prophylaxis. In vitro, the combination of b12, 2G12, 2F5 and 4E10 potently neutralized primary HIV isolates of clades A, B, C, and D. Our data suggest that Passive Immunization with currently available anti-HIV clade B nmAbs could play a role in preventing transmission of non-clade B isolates through breastfeeding. We furthermore conclude that the epitopes recognized by the nmAbs in our successful Passive Immunization studies are important determinants for protection and provide targets for developing neutralizing antibody-response-based, active AIDS vaccines.

  • Passive Immunization with human neutralizing monoclonal antibodies correlates of protective immunity against hiv
    Nobel Symposium, 2002
    Co-Authors: Regina Hofmannlehmann, Harold M. Mcclure, Ruth M. Ruprecht
    Abstract:

    Passive Immunization with synergistic combinations of human monoclonal antibodies (mAbs) directed against conserved epitopes of the human immunodeficiency virus (HIV) envelope completely protected 13 out of 16 rhesus monkeys challenged intravenously or orally with chimeric simian-human immunodeficiency virus (SHIV) strains; partial protection was seen in another two. A high degree of protection was seen among orally challenged neonates. Thus, we propose that Passive Immunization with synergistic combinations of neutralizing human mAbs may be effective in preventing maternal HIV transmission when given as post-exposure prophylaxis at birth and as prophylaxis against milk-borne transmission. Because we only used mAbs with well-defined epitope specificities, our studies also yield key information for designing AIDS vaccines: the correlates of immune protection. Vaccine strategies that can evoke antibody responses to epitopes recognized by the mAbs used in our primate studies could be important components of successful AIDS vaccines.

Lars M. Ittner - One of the best experts on this subject based on the ideXlab platform.

  • Tau-targeting Passive Immunization modulates aspects of pathology in tau transgenic mice
    Journal of neurochemistry, 2014
    Co-Authors: Arne Ittner, Josefine Bertz, Lisa S. Suh, Claire H. Stevens, Jürgen Götz, Lars M. Ittner
    Abstract:

    Immunization is increasingly recognized as a suitable therapeutic avenue for the treatment of neurological diseases such as Alzheimer's disease and other tauopathies. Tau is a key molecular player in these conditions and therefore represents an attractive target for Passive Immunization approaches. We performed such an approach in two independent tau transgenic mouse models of tauopathy, K369I tau transgenic K3 and P301L tau transgenic pR5 mice. The antibodies we used were either specific for full-length tau or tau phosphorylated at serine 404 (pS404), a residue that forms part of the paired helical filament (PHF)-1 phosphoepitope that characterizes tau neurofibrillary tangles in tauopathies. Although both pS404 antibodies had a similar affinity, they differed in isotype, and only Passive Immunization with the IgG2a/κ pS404-specific antibody resulted in a lower tangle burden and reduced phosphorylation of tau at the PHF1 epitope in K3 mice. In pR5 mice, the same antibody led to a reduced phosphorylation of the pS422 and PHF1 epitopes of tau. In addition, histological sections of the hippocampal dentate gyrus of the immunized pR5 mice displayed reduced pS422 staining intensities. These results show that Passive Immunization targeting tau can modulate aspects of tau pathology in tau transgenic mouse models, in an antibody isotype-specific manner.