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  1. Article ; Online: Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

    Howard, Leigh M / Jensen, Travis L / Goll, Johannes B / Gelber, Casey E / Bradley, Matthew D / Sherrod, Stacy D / Hoek, Kristen L / Yoder, Sandra / Jimenez-Truque, Natalia / Edwards, Kathryn / Creech, C Buddy

    The Journal of infectious diseases

    2024  

    Abstract: Background: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.: Methods: Twenty healthy men and women (18-49 years of age) were ... ...

    Abstract Background: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.
    Methods: Twenty healthy men and women (18-49 years of age) were randomized to receive two doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) one month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization.
    Results: Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any post-vaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on Day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without.
    Conclusions: Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines.
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad611
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures.

    Hamzabegovic, Fahreta / Goll, Johannes B / Hooper, William F / Frey, Sharon / Gelber, Casey E / Abate, Getahun

    NPJ vaccines

    2020  Volume 5, Issue 1, Page(s) 6

    Abstract: ... Yersinia ... ...

    Abstract Yersinia pestis
    Keywords covid19
    Language English
    Publishing date 2020-01-23
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-020-0156-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Corrigendum: The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies.

    Goll, Johannes B / Bosinger, Steven E / Jensen, Travis L / Walum, Hasse / Grimes, Tyler / Tharp, Gregory K / Natrajan, Muktha S / Blazevic, Azra / Head, Richard D / Gelber, Casey E / Steenbergen, Kristen J / Patel, Nirav B / Sanz, Patrick / Rouphael, Nadine G / Anderson, Evan J / Mulligan, Mark J / Hoft, Daniel F

    Frontiers in immunology

    2023  Volume 14, Page(s) 1163550

    Abstract: This corrects the article DOI: 10.3389/fimmu.2022.1093242.]. ...

    Abstract [This corrects the article DOI: 10.3389/fimmu.2022.1093242.].
    Language English
    Publishing date 2023-02-23
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1163550
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies.

    Goll, Johannes B / Bosinger, Steven E / Jensen, Travis L / Walum, Hasse / Grimes, Tyler / Tharp, Gregory K / Natrajan, Muktha S / Blazevic, Azra / Head, Richard D / Gelber, Casey E / Steenbergen, Kristen J / Patel, Nirav B / Sanz, Patrick / Rouphael, Nadine G / Anderson, Evan J / Mulligan, Mark J / Hoft, Daniel F

    Frontiers in immunology

    2023  Volume 13, Page(s) 1093242

    Abstract: Introduction: Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. The goal of ... ...

    Abstract Introduction: Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. The goal of this study was to benchmark key technical and analytical parameters of RNA sequencing (RNA-seq) in the context of a multi-site, double-blind randomized vaccine clinical trial.
    Methods: We collected longitudinal peripheral blood mononuclear cell (PBMC) samples from 10 subjects before and after vaccination with a live attenuated
    Results and discussion: Our results showed that (i) filtering lowly-expressed genes is recommended to improve fold-change accuracy and inter-site agreement, if possible guided by mRNA spike-ins (ii) read length did not have a major impact on DEG detection, (iii) applying fold-change cutoffs for DEG detection reduced inter-set agreement and should be used with caution, if at all, (iv) reduction in sequencing depth had a minimal impact on statistical power but reduced the identifiable fraction of the PBMC transcriptome, (v) after sample size, effect size (i.e. the magnitude of fold change) was the most important driver of statistical power to detect DEG. The results from this study provide RNA sequencing benchmarks and guidelines for planning future similar vaccine studies.
    MeSH term(s) Humans ; RNA-Seq ; Benchmarking ; Leukocytes, Mononuclear ; Vaccines, Attenuated ; RNA, Messenger/genetics
    Chemical Substances Vaccines, Attenuated ; RNA, Messenger
    Language English
    Publishing date 2023-01-19
    Publishing country Switzerland
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1093242
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The antibody landscapes following AS03 and MF59 adjuvanted H5N1 vaccination.

    Goll, Johannes B / Jain, Aarti / Jensen, Travis L / Assis, Rafael / Nakajima, Rie / Jasinskas, Algis / Coughlan, Lynda / Cherikh, Sami R / Gelber, Casey E / Khan, S / Huw Davies, D / Meade, Philip / Stadlbauer, Daniel / Strohmeier, Shirin / Krammer, Florian / Chen, Wilbur H / Felgner, Philip L

    NPJ vaccines

    2022  Volume 7, Issue 1, Page(s) 103

    Abstract: Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, ... ...

    Abstract Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays (NCT01317758 and NCT01317745). The arrays were designed to reflect both full-length and globular head HA derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and heterosubtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. The adjuvanted vaccine was also associated with the elicitation of stalk-directed antibody. We established good correlation of the array antibody responses to H5 antigens with standard HA inhibition and microneutralization titers.
    Language English
    Publishing date 2022-08-30
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-022-00524-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cytomegalovirus Genetic Diversity Following Primary Infection.

    Ross, Shannon A / Pati, Pravasini / Jensen, Travis L / Goll, Johannes B / Gelber, Casey E / Singh, Amy / McNeal, Monica / Boppana, Suresh B / Bernstein, David I

    The Journal of infectious diseases

    2019  Volume 221, Issue 5, Page(s) 715–720

    Abstract: Background: Infection with multiple cytomegalovirus (CMV) strains (mixed infection) was reported in a variety of hosts. As the virus genetic diversity in primary CMV infection and the changes over time remain incompletely defined, we examined CMV ... ...

    Abstract Background: Infection with multiple cytomegalovirus (CMV) strains (mixed infection) was reported in a variety of hosts. As the virus genetic diversity in primary CMV infection and the changes over time remain incompletely defined, we examined CMV diversity and changes in diversity over time in healthy adolescent females who participated in a phase 2 CMV gB/MF59 vaccine trial.
    Methods: CMV genetic diversity was determined by genotyping of 5 genes-gB (UL55), gH (UL75), gN (UL73), US28, and UL144-in urine, saliva, and plasma samples from 15 study subjects.
    Results: At the time of primary infection, 5 of 12 (42%) urine samples had multiple virus strains, and 50% of vaccine recipients were infected with gB1 genotype (vaccine strain). Mixed infection was documented in all 15 subjects within 3 months after primary infection, and the majority had different CMV genotypes in different compartments. Changes in genotypes over time were observed in all subjects.
    Conclusions: Infection with multiple CMV genotypes was common during primary infection and further diversification occurred over time. Infection with gB1 genotype in vaccine recipients suggests a lack of strain-specific protection from the vaccine. As only 5 polymorphic genes were assessed, this study likely underestimated the true genetic diversity in primary CMV infection.
    MeSH term(s) Adolescent ; Coinfection/diagnosis ; Coinfection/virology ; Cytomegalovirus/genetics ; Cytomegalovirus Infections/diagnosis ; Cytomegalovirus Infections/prevention & control ; Cytomegalovirus Infections/virology ; Cytomegalovirus Vaccines/therapeutic use ; Double-Blind Method ; Female ; Genotype ; Humans ; Membrane Glycoproteins/blood ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/urine ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction ; Receptors, Chemokine/blood ; Receptors, Chemokine/genetics ; Saliva/virology ; Vaccination ; Viral Envelope Proteins/blood ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/urine ; Viral Load ; Viral Proteins/blood ; Viral Proteins/genetics ; Viral Proteins/urine
    Chemical Substances Cytomegalovirus Vaccines ; Membrane Glycoproteins ; Receptors, Chemokine ; UL144 ORF protein, Human herpesvirus 5 ; US28 receptor, Cytomegalovirus ; Viral Envelope Proteins ; Viral Proteins
    Language English
    Publishing date 2019-10-07
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiz507
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Proteomic Analysis of Human Immune Responses to Live-Attenuated Tularemia Vaccine.

    Chang, Yie-Hwa / Duong, Duc M / Goll, Johannes B / Wood, David C / Jensen, Travis L / Yin, Luming / Gelber, Casey E / Seyfried, Nicholas T / Anderson, Evan / Natrajan, Muktha S / Rouphael, Nadine / Johnson, Robert A / Sanz, Patrick / Mulligan, Mark J / Hoft, Daniel F

    Vaccines

    2020  Volume 8, Issue 3

    Abstract: Francisella ... ...

    Abstract Francisella tularensis
    Language English
    Publishing date 2020-07-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines8030413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Transcriptomic and Metabolic Responses to a Live-Attenuated

    Goll, Johannes B / Li, Shuzhao / Edwards, James L / Bosinger, Steven E / Jensen, Travis L / Wang, Yating / Hooper, William F / Gelber, Casey E / Sanders, Katherine L / Anderson, Evan J / Rouphael, Nadine / Natrajan, Muktha S / Johnson, Robert A / Sanz, Patrick / Hoft, Daniel / Mulligan, Mark J

    Vaccines

    2020  Volume 8, Issue 3

    Abstract: The immune response to live- ... ...

    Abstract The immune response to live-attenuated
    Language English
    Publishing date 2020-07-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines8030412
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: AS03-Adjuvanted H5N1 Avian Influenza Vaccine Modulates Early Innate Immune Signatures in Human Peripheral Blood Mononuclear Cells.

    Howard, Leigh M / Goll, Johannes B / Jensen, Travis L / Hoek, Kristen L / Prasad, Nripesh / Gelber, Casey E / Levy, Shawn E / Joyce, Sebastian / Link, Andrew J / Creech, C Buddy / Edwards, Kathryn M

    The Journal of infectious diseases

    2018  Volume 219, Issue 11, Page(s) 1786–1798

    Abstract: Background: Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood.: Methods: Using ribonucleic acid sequencing on peripheral blood mononuclear cells ( ... ...

    Abstract Background: Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood.
    Methods: Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types.
    Results: AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs.
    Conclusions: Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.
    MeSH term(s) Adaptive Immunity ; Adjuvants, Immunologic/therapeutic use ; Adult ; Double-Blind Method ; Drug Combinations ; Gene Expression Profiling ; Humans ; Immunity, Innate ; Influenza A Virus, H5N1 Subtype/immunology ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Influenza, Human/virology ; Leukocytes/immunology ; Polysorbates ; Signal Transduction ; Squalene/immunology ; Young Adult ; alpha-Tocopherol/immunology
    Chemical Substances Adjuvants, Immunologic ; Drug Combinations ; Influenza Vaccines ; Polysorbates ; Squalene (7QWM220FJH) ; AS03 adjuvant (A7YT618XBV) ; alpha-Tocopherol (H4N855PNZ1)
    Language English
    Publishing date 2018-12-13
    Publishing country United States
    Document type Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiy721
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents.

    Hornik, Christoph P / Yogev, Ram / Mourani, Peter M / Watt, Kevin M / Sullivan, Janice E / Atz, Andrew M / Speicher, David / Al-Uzri, Amira / Adu-Darko, Michelle / Payne, Elizabeth H / Gelber, Casey E / Lin, Susan / Harper, Barrie / Melloni, Chiara / Cohen-Wolkowiez, Michael / Gonzalez, Daniel

    Journal of clinical pharmacology

    2019  Volume 59, Issue 12, Page(s) 1606–1619

    Abstract: Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction ... ...

    Abstract Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction of critical illness. We developed a population pharmacokinetic model of milrinone using nonlinear mixed-effects modeling in NONMEM to perform dose-exposure simulations in children with variable renal function. We included children aged <21 years who received intravenous milrinone per clinical care. Plasma milrinone concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay (range 1-5000 ng/mL). We performed dose-exposure simulations targeting steady-state therapeutic concentrations of 100-300 ng/mL previously established in adults and children with cardiac dysfunction. We simulated concentrations over 48 hours in typical subjects with decreasing creatinine clearance (CrCl), estimated using the updated bedside Schwartz equation. Seventy-four patients contributed 111 plasma samples (concentration range, 4-634 ng/mL). The median (range) postmenstrual age (PMA) was 3.7 years (0-18), and median weight (WT) was 13.1 kg (2.6-157.7). The median serum creatinine and CrCl were 0.5 mg/dL (0.1-3.1) and 117.2 mL/min/1.73 m
    MeSH term(s) Adolescent ; Cardiac Output/drug effects ; Cardiotonic Agents/pharmacokinetics ; Child ; Creatinine/blood ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Milrinone/pharmacokinetics ; Vasodilator Agents/pharmacokinetics
    Chemical Substances Cardiotonic Agents ; Vasodilator Agents ; Creatinine (AYI8EX34EU) ; Milrinone (JU9YAX04C7)
    Language English
    Publishing date 2019-07-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 188980-1
    ISSN 1552-4604 ; 0091-2700 ; 0021-9754
    ISSN (online) 1552-4604
    ISSN 0091-2700 ; 0021-9754
    DOI 10.1002/jcph.1499
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