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  1. Article: Protection against Severe Illness versus Immunity-Redefining Vaccine Effectiveness in the Aftermath of COVID-19.

    Roche, Renuka / Odeh, Nouha H / Andar, Abhay U / Tulapurkar, Mohan E / Roche, Joseph A

    Microorganisms

    2023  Volume 11, Issue 8

    Abstract: Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, ... ...

    Abstract Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, individuals who were fully vaccinated did get infected in high numbers, and viral loads in vaccinated individuals were as high as those in the unvaccinated. However, even with high viral loads, vaccinated individuals were significantly less likely to develop severe illness; this begs the question as to whether the main effect of anti-SARS-CoV-2 vaccines is to confer protection against severe illness or immunity against infection. The answer to this question is consequential, not only to the understanding of how anti-SARS-CoV-2 vaccines work, but also to public health efforts against existing and novel pathogens. In this review, we argue that immune system sensitization-desensitization rather than sterilizing immunity may explain vaccine-mediated protection against severe COVID-19 illness even when the SARS-CoV-2 viral load is high. Through the lessons learned from COVID-19, we make the case that in the disease's aftermath, public health agencies must revisit healthcare policies, including redefining the term "vaccine effectiveness."
    Language English
    Publishing date 2023-07-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms11081963
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Microneedle-Assisted Skin Permeation by Nontoxic Bioengineerable Gas Vesicle Nanoparticles.

    Andar, Abhay U / Karan, Ram / Pecher, Wolf T / DasSarma, Priya / Hedrich, William D / Stinchcomb, Audra L / DasSarma, Shiladitya

    Molecular pharmaceutics

    2017  Volume 14, Issue 3, Page(s) 953–958

    Abstract: Gas vesicle nanoparticles (GVNPs) are hollow, buoyant protein organelles produced by the extremophilic microbe Halobacterium sp. NRC-1 and are being developed as bioengineerable and biocompatible antigen and drug-delivery systems (DDS). Dynamic light ... ...

    Abstract Gas vesicle nanoparticles (GVNPs) are hollow, buoyant protein organelles produced by the extremophilic microbe Halobacterium sp. NRC-1 and are being developed as bioengineerable and biocompatible antigen and drug-delivery systems (DDS). Dynamic light scattering measurements of purified GVNP suspensions showed a mean diameter of 245 nm. In vitro diffusion studies using Yucatan miniature pig skin showed GVNP permeation to be enhanced after MN-treatment compared to untreated skin. GVNPs were found to be nontoxic to mammalian cells (human kidney and rat mycocardial myoblasts). These findings support the use of GVNPs as DDS for intradermal/transdermal permeation of protein- and peptide-based drugs.
    MeSH term(s) Administration, Cutaneous ; Animals ; Diffusion ; Drug Carriers/administration & dosage ; Drug Delivery Systems/methods ; Dynamic Light Scattering/methods ; Gases/administration & dosage ; Humans ; Mammals/metabolism ; Nanoparticles/administration & dosage ; Needles ; Permeability ; Pharmaceutical Preparations/administration & dosage ; Rats ; Skin/metabolism ; Skin Absorption/physiology ; Swine
    Chemical Substances Drug Carriers ; Gases ; Pharmaceutical Preparations
    Language English
    Publishing date 2017--06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.6b00859
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Microfluidic preparation of liposomes to determine particle size influence on cellular uptake mechanisms.

    Andar, Abhay U / Hood, Renee R / Vreeland, Wyatt N / Devoe, Don L / Swaan, Peter W

    Pharmaceutical research

    2013  Volume 31, Issue 2, Page(s) 401–413

    Abstract: Purpose: This study investigates the cellular uptake and trafficking of liposomes in Caco-2 cells, using vesicles with distinct average diameters ranging from 40.6 nm to 276.6 nm. Liposomes were prepared by microfluidic hydrodynamic flow focusing, ... ...

    Abstract Purpose: This study investigates the cellular uptake and trafficking of liposomes in Caco-2 cells, using vesicles with distinct average diameters ranging from 40.6 nm to 276.6 nm. Liposomes were prepared by microfluidic hydrodynamic flow focusing, producing nearly-monodisperse populations and enabling size-dependent uptake to be effectively evaluated.
    Methods: Populations of PEG-conjugated liposomes of various distinct sizes were prepared in a disposable microfluidic device using a simple continuous-flow microfluidic technique. Liposome cellular uptake was investigated using flow cytometry and confocal microscopy.
    Results: Liposome uptake by Caco-2 cells was observed to be strongly size-dependent for liposomes with mean diameters ranging from 40.6 nm to 276.6 nm. When testing these liposomes against endocytosis inhibitors, cellular uptake of the largest (97.8 nm and 162.1 nm in diameter) liposomes were predominantly subjected to clathrin-dependent uptake mechanisms, the medium-sized (72.3 nm in diameter) liposomes seemed to be influenced by all investigated pathways and the smallest liposomes (40.6 nm in diameter) primarily followed a dynamin-dependent pathway. In addition, the 40.6 nm, 72.3 nm, and 162.1 nm diameter liposomes showed slightly decreased accumulation within endosomes after 1 h compared to liposomes which were 97.8 nm in diameter. Conversely, liposome co-localization with lysosomes was consistent for liposomes ranging from 40.6 nm to 97.8 nm in diameter.
    Conclusions: The continuous-flow synthesis of nearly-monodisperse populations of liposomes of distinct size via a microfluidic hydrodynamic flow focusing technique enabled unique in vitro studies in which specific effects of particle size on cellular uptake were elucidated. The results of this study highlight the significant influence of liposome size on cellular uptake mechanisms and may be further exploited for increasing specificity, improving efficacy, and reducing toxicity of liposomal drug delivery systems.
    MeSH term(s) Caco-2 Cells ; Cell Line, Tumor ; Clathrin/chemistry ; Clathrin/metabolism ; Drug Delivery Systems/methods ; Dynamins/chemistry ; Dynamins/metabolism ; Endocytosis/physiology ; Humans ; Liposomes/chemistry ; Liposomes/metabolism ; Microfluidics/methods ; Particle Size ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/metabolism
    Chemical Substances Clathrin ; Liposomes ; Polyethylene Glycols (3WJQ0SDW1A) ; Dynamins (EC 3.6.5.5)
    Language English
    Publishing date 2013-10-03
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 843063-9
    ISSN 1573-904X ; 0724-8741 ; 0739-0742
    ISSN (online) 1573-904X
    ISSN 0724-8741 ; 0739-0742
    DOI 10.1007/s11095-013-1171-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1937: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Low-cost customizable microscale toolkit for rapid screening and purification of therapeutic proteins.

    Andar, Abhay U / Deldari, Sevda / Gutierrez, Erick / Burgenson, David / Al-Adhami, Mustafa / Gurramkonda, Chandrasekhar / Tolosa, Leah / Kostov, Yordan / Frey, Douglas D / Rao, Govind

    Biotechnology and bioengineering

    2018  Volume 116, Issue 4, Page(s) 870–881

    Abstract: Biopharmaceutical separations require tremendous amounts of optimization to achieve acceptable product purity. Typically, large volumes of reagents and biological materials are needed for testing different parameters, thus adding to the expense of ... ...

    Abstract Biopharmaceutical separations require tremendous amounts of optimization to achieve acceptable product purity. Typically, large volumes of reagents and biological materials are needed for testing different parameters, thus adding to the expense of biopharmaceutical process development. This study demonstrates a versatile and customizable microscale column (µCol) for biopharmaceutical separations using immobilized metal affinity chromatography (IMAC) as an example application to identify key parameters. µCols have excellent precision, efficiency, and reproducibility, can accommodate any affinity, ion-exchange or size-exclusion-based resin and are compatible with any high-performance liquid chromatography (HPLC) system. µCols reduce reagent amounts, provide comparable purification performance and high-throughput, and are easy to automate compared with current conventional resin columns. We provide a detailed description of the fabrication methods, resin packing methods, and µCol validation experiments using a conventional HPLC system. Finite element modeling using COMSOL Multiphysics was used to validate the experimental performance of the µCols. In this study, µCols were used for improving the purification achieved for granulocyte colony stimulating factor (G-CSF) expressed using a cell-free CHO in vitro translation (IVT) system and were compared to a conventional 1 ml IMAC column. Experimental data revealed comparable purity with a 10-fold reduction in the amount of buffer, resin, and purification time for the μCols compared with conventional columns for similar protein yields.
    MeSH term(s) Algorithms ; Animals ; CHO Cells ; Chromatography, Affinity/economics ; Chromatography, Affinity/instrumentation ; Chromatography, High Pressure Liquid/economics ; Chromatography, High Pressure Liquid/instrumentation ; Cricetulus ; Equipment Design ; Granulocyte Colony-Stimulating Factor/isolation & purification
    Chemical Substances Granulocyte Colony-Stimulating Factor (143011-72-7)
    Language English
    Publishing date 2018-12-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 280318-5
    ISSN 1097-0290 ; 0006-3592
    ISSN (online) 1097-0290
    ISSN 0006-3592
    DOI 10.1002/bit.26876
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.B 960: Show issues Location:
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  5. Article ; Online: Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity, and protection across serotypes.

    Heine, Shannon J / Diaz-McNair, Jovita / Andar, Abhay U / Drachenberg, Cinthia B / van de Verg, Lillian / Walker, Richard / Picking, Wendy L / Pasetti, Marcela F

    Journal of immunology (Baltimore, Md. : 1950)

    2014  Volume 192, Issue 4, Page(s) 1630–1640

    Abstract: Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type ... ...

    Abstract Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25-40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.
    MeSH term(s) Animals ; Antigens, Bacterial/administration & dosage ; Antigens, Bacterial/immunology ; Bacterial Proteins/administration & dosage ; Bacterial Proteins/immunology ; Bacterial Toxins/immunology ; Cell Movement/immunology ; Cross Protection/immunology ; Cytokines/metabolism ; Dendritic Cells/immunology ; Drug Delivery Systems ; Dysentery, Bacillary/immunology ; Dysentery, Bacillary/prevention & control ; Enterotoxins/immunology ; Escherichia coli/immunology ; Escherichia coli Proteins/immunology ; Female ; Immunoglobulin A/blood ; Immunoglobulin A/immunology ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Langerhans Cells/immunology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Neutrophils/immunology ; Shigella Vaccines/administration & dosage ; Shigella Vaccines/immunology ; Shigella flexneri/immunology ; Shigella sonnei/immunology ; Vaccines, Subunit/administration & dosage ; Vaccines, Subunit/immunology
    Chemical Substances Antigens, Bacterial ; Bacterial Proteins ; Bacterial Toxins ; Cytokines ; Enterotoxins ; Escherichia coli Proteins ; Immunoglobulin A ; Immunoglobulin G ; IpaD protein, Shigella flexneri ; Shigella Vaccines ; Vaccines, Subunit ; ipaB protein, Shigella (127384-62-7) ; heat-labile enterotoxin, E coli (D9K3SN2LNY)
    Language English
    Publishing date 2014-01-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1302743
    Database MEDical Literature Analysis and Retrieval System OnLINE

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