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  1. Article ; Online: Programming cytomegalovirus as an HIV vaccine.

    Picker, Louis J / Lifson, Jeffrey D / Gale, Michael / Hansen, Scott G / Früh, Klaus

    Trends in immunology

    2023  Volume 44, Issue 4, Page(s) 287–304

    Abstract: The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, ... ...

    Abstract The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, CD8
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes ; AIDS Vaccines ; Simian Acquired Immunodeficiency Syndrome/prevention & control ; Cytomegalovirus ; Simian Immunodeficiency Virus ; Cytomegalovirus Infections
    Chemical Substances AIDS Vaccines
    Language English
    Publishing date 2023-03-07
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2023.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reply to Viel.

    Recknor, Christopher / Hansen, Scott G / Gaylis, Norman B / Tiwary, Meenakshi / Sacha, Jonah B / Yang, Otto O

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2022  Volume 75, Issue 8, Page(s) 1486–1487

    Language English
    Publishing date 2022-07-09
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciac390
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  3. Article: Pre-challenge gut microbial signature predicts RhCMV/SIV vaccine efficacy in rhesus macaques.

    Brochu, Hayden N / Smith, Elise / Jeong, Sangmi / Carlson, Michelle / Hansen, Scott G / Tisoncik-Go, Jennifer / Law, Lynn / Picker, Louis J / Gale, Michael / Peng, Xinxia

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Background: RhCMV/SIV vaccines protect ∼59% of vaccinated rhesus macaques against repeated limiting-dose intra-rectal exposure with highly pathogenic SIVmac239M, but the exact mechanism responsible for the vaccine efficacy is not known. It is becoming ... ...

    Abstract Background: RhCMV/SIV vaccines protect ∼59% of vaccinated rhesus macaques against repeated limiting-dose intra-rectal exposure with highly pathogenic SIVmac239M, but the exact mechanism responsible for the vaccine efficacy is not known. It is becoming evident that complex interactions exist between gut microbiota and the host immune system. Here we aimed to investigate if the rhesus gut microbiome impacts RhCMV/SIV vaccine-induced protection.
    Methods: Three groups of 15 rhesus macaques naturally pre-exposed to RhCMV were vaccinated with RhCMV/SIV vaccines. Rectal swabs were collected longitudinally both before SIV challenge (after vaccination) and post challenge and were profiled using 16S rRNA based microbiome analysis.
    Results: We identified ∼2,400 16S rRNA amplicon sequence variants (ASVs), representing potential bacterial species/strains. Global gut microbial profiles were strongly associated with each of the three vaccination groups, and all animals tended to maintain consistent profiles throughout the pre-challenge phase. Despite vaccination group differences, using newly developed compositional data analysis techniques we identified a common gut microbial signature predictive of vaccine protection outcome across the three vaccination groups. Part of this microbial signature persisted even after SIV challenge. We also observed a strong correlation between this microbial signature and an early signature derived from whole blood transcriptomes in the same animals.
    Conclusions: Our findings indicate that changes in gut microbiomes are associated with RhCMV/SIV vaccine-induced protection and early host response to vaccination in rhesus macaques.
    Language English
    Publishing date 2024-02-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.27.582186
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: BFF and cellhashR: analysis tools for accurate demultiplexing of cell hashing data.

    Boggy, Gregory J / McElfresh, G W / Mahyari, Eisa / Ventura, Abigail B / Hansen, Scott G / Picker, Louis J / Bimber, Benjamin N

    Bioinformatics (Oxford, England)

    2022  Volume 38, Issue 10, Page(s) 2791–2801

    Abstract: Motivation: Single-cell sequencing methods provide previously impossible resolution into the transcriptome of individual cells. Cell hashing reduces single-cell sequencing costs by increasing capacity on droplet-based platforms. Cell hashing methods ... ...

    Abstract Motivation: Single-cell sequencing methods provide previously impossible resolution into the transcriptome of individual cells. Cell hashing reduces single-cell sequencing costs by increasing capacity on droplet-based platforms. Cell hashing methods rely on demultiplexing algorithms to accurately classify droplets; however, assumptions underlying these algorithms limit accuracy of demultiplexing, ultimately impacting the quality of single-cell sequencing analyses.
    Results: We present Bimodal Flexible Fitting (BFF) demultiplexing algorithms BFFcluster and BFFraw, a novel class of algorithms that rely on the single inviolable assumption that barcode count distributions are bimodal. We integrated these and other algorithms into cellhashR, a new R package that provides integrated QC and a single command to execute and compare multiple demultiplexing algorithms. We demonstrate that BFFcluster demultiplexing is both tunable and insensitive to issues with poorly behaved data that can confound other algorithms. Using two well-characterized reference datasets, we demonstrate that demultiplexing with BFF algorithms is accurate and consistent for both well-behaved and poorly behaved input data.
    Availability and implementation: cellhashR is available as an R package at https://github.com/BimberLab/cellhashR. cellhashR version 1.0.3 was used for the analyses in this manuscript and is archived on Zenodo at https://www.doi.org/10.5281/zenodo.6402477.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Algorithms ; Electronic Data Processing ; Sequence Analysis ; Single-Cell Analysis ; Software
    Language English
    Publishing date 2022-05-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btac213
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  5. Article: Quantification of T cell Antigen-specific Memory Responses in Rhesus Macaques, Using Cytokine Flow Cytometry (CFC, also Known as ICS and ICCS): Analysis of Flow Data.

    Sylwester, Andrew W / Hansen, Scott G / Picker, Louis J

    Bio-protocol

    2017  Volume 4, Issue 8

    Abstract: What was initially termed 'CFC' (Cytokine Flow Cytometry) is now more commonly known as 'ICS' (Intra Cellular Staining), or less commonly as 'ICCS' (Intra Cellular Cytokine Staining). The key innovations were use of an effective permeant (allowing ... ...

    Abstract What was initially termed 'CFC' (Cytokine Flow Cytometry) is now more commonly known as 'ICS' (Intra Cellular Staining), or less commonly as 'ICCS' (Intra Cellular Cytokine Staining). The key innovations were use of an effective permeant (allowing intracellular staining), and a reagent to disrupt secretion (trapping cytokines, thereby enabling accumulation of detectable intracellular signal). Because not all researchers who use the technique are interested in cytokines, the 'ICS' term has gained favor, though 'CFC' will be used here. CFC is a test of cell function, exposing lymphocytes to antigen in culture, then measuring any cytokine responses elicited. Test cultures are processed so as to stain cells with monoclonal antibodies tagged with fluorescent markers, and to chemically fix the cells and decontaminate the samples, using paraformaldehyde. CFC provides the powers of flow cytometry, which includes bulk sampling and multi-parametric cross-correlation, to the analysis of antigen-specific memory responses. A researcher using CFC is able to phenotypically characterize cells cultured with test antigen, and for phenotypic subsets (e.g. CD4
    Language English
    Publishing date 2017-03-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.1109
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  6. Article ; Online: Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome.

    Gaylis, Norman B / Ritter, Angela / Kelly, Scott A / Pourhassan, Nader Z / Tiwary, Meenakshi / Sacha, Jonah B / Hansen, Scott G / Recknor, Christopher / Yang, Otto O

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2022  Volume 75, Issue 7, Page(s) 1232–1234

    Abstract: In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These ... ...

    Abstract In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab. Clinical Trials Registration. NCT04678830.
    MeSH term(s) COVID-19 ; Chemokines, CC ; Humans ; Immunosuppression Therapy ; Receptors, CCR5
    Chemical Substances Chemokines, CC ; Receptors, CCR5
    Language English
    Publishing date 2022-04-22
    Publishing country United States
    Document type Clinical Trial ; Journal Article
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciac226
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  7. Article: Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity.

    Otero, Claire E / Petkova, Sophia / Ebermann, Martin / Taher, Husam / John, Nessy / Hoffmann, Katja / Davalos, Angel / Moström, Matilda J / Gilbride, Roxanne M / Papen, Courtney R / Barber-Axthelm, Aaron / Scheef, Elizabeth A / Barfield, Richard / Sprehe, Lesli M / Kendall, Savannah / Manuel, Tabitha D / Vande Burgt, Nathan H / Chan, Cliburn / Denton, Michael /
    Streblow, Zachary J / Streblow, Daniel N / Hansen, Scott G / Kaur, Amitinder / Permar, Sallie / Früh, Klaus / Hengel, Hartmut / Malouli, Daniel / Kolb, Philipp

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated ... ...

    Abstract Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation
    Language English
    Publishing date 2024-02-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.27.582371
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: The pentameric complex is not required for vertical transmission of cytomegalovirus in seronegative pregnant rhesus macaques.

    Wang, Hsuan-Yuan / Taher, Husam / Kreklywich, Craig N / Schmidt, Kimberli A / Scheef, Elizabeth A / Barfield, Richard / Otero, Claire E / Valencia, Sarah M / Crooks, Chelsea M / Mirza, Anne / Woods, Kelsey / Burgt, Nathan Vande / Kowalik, Timothy F / Barry, Peter A / Hansen, Scott G / Tarantal, Alice F / Chan, Cliburn / Streblow, Daniel N / Picker, Louis J /
    Kaur, Amitinder / Früh, Klaus / Permar, Sallie R / Malouli, Daniel

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neonatal neurological impairment but essential virological determinants of transplacental CMV transmission remain unclear. The pentameric complex (PC), composed of five ... ...

    Abstract Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neonatal neurological impairment but essential virological determinants of transplacental CMV transmission remain unclear. The pentameric complex (PC), composed of five subunits, glycoproteins H (gH), gL, UL128, UL130, and UL131A, is essential for efficient entry into non-fibroblast cells
    One sentence summary: Congenital CMV transmission frequency in seronegative rhesus macaques is not affected by the deletion of the viral pentameric complex.
    Language English
    Publishing date 2023-06-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.15.545169
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Systematic Profiling of Full-Length Ig and TCR Repertoire Diversity in Rhesus Macaque through Long Read Transcriptome Sequencing.

    Brochu, Hayden N / Tseng, Elizabeth / Smith, Elise / Thomas, Matthew J / Jones, Aiden M / Diveley, Kayleigh R / Law, Lynn / Hansen, Scott G / Picker, Louis J / Gale, Michael / Peng, Xinxia

    Journal of immunology (Baltimore, Md. : 1950)

    2020  Volume 204, Issue 12, Page(s) 3434–3444

    Abstract: The diversity of Ig and TCR repertoires is a focal point of immunological studies. Rhesus macaques ( ...

    Abstract The diversity of Ig and TCR repertoires is a focal point of immunological studies. Rhesus macaques (
    MeSH term(s) Animals ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Immunoglobulins/genetics ; Immunoglobulins/immunology ; Macaca mulatta/genetics ; Macaca mulatta/immunology ; Receptors, Antigen, T-Cell/immunology ; Transcriptome/genetics ; Transcriptome/immunology
    Chemical Substances Immunoglobulins ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2020-05-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    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.1901256
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  10. Article ; Online: New paradigms for HIV/AIDS vaccine development.

    Picker, Louis J / Hansen, Scott G / Lifson, Jeffrey D

    Annual review of medicine

    2011  Volume 63, Page(s) 95–111

    Abstract: HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution to evade host immunity. By virtue of specific adaptations that thwart individual innate or adaptive immune mechanisms, and an overall replication strategy that provides for ... ...

    Abstract HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution to evade host immunity. By virtue of specific adaptations that thwart individual innate or adaptive immune mechanisms, and an overall replication strategy that provides for rapid establishment of a large, systemic viral population, capable of dynamic adaptation to almost all immune selection pressures, these viruses, once established, almost invariably stay one step ahead of the host's immune system, and in the vast majority of infected individuals, replicate indefinitely. Although many vaccine approaches tested to date have been able to enhance the magnitude of the immune responses to HIV/SIV infection, most of these responses, whether cellular or humoral, have largely failed to be both effectively antiviral and targeted to prevent the emergence of fully functional escape variants. Recent advances, however, have provided strong evidence that the initial stages of infection following mucosal transmission of these viruses are more vulnerable to immune intervention, and have led to the development of vaccine strategies that elicit responses able to effectively intervene in these early stages of infection, either preventing acquisition of infection or establishing early, stringent, and durable control. Here, we place HIV/AIDS vaccine development in the context of the basic immunobiology of HIV and SIV, review the evidence for their vulnerability to immune responses immediately after mucosal transmission, and discuss how this newly recognized vulnerability might be exploited for the development of an effective HIV/AIDS vaccine.
    MeSH term(s) AIDS Vaccines/immunology ; Acquired Immunodeficiency Syndrome/immunology ; Acquired Immunodeficiency Syndrome/prevention & control ; Allergy and Immunology/trends ; Humans
    Chemical Substances AIDS Vaccines
    Language English
    Publishing date 2011-09-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 207930-6
    ISSN 1545-326X ; 0066-4219
    ISSN (online) 1545-326X
    ISSN 0066-4219
    DOI 10.1146/annurev-med-042010-085643
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