5 results on '"C Buddy Creech"'
Search Results
2. AS03-Adjuvanted H5N1 Avian Influenza Vaccine Modulates Early Innate Immune Signatures in Human Peripheral Blood Mononuclear Cells
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C. Buddy Creech, Travis L. Jensen, Casey E. Gelber, Andrew J. Link, Kristen L. Hoek, Kathryn M. Edwards, Leigh M Howard, Shawn Levy, Sebastian Joyce, Nripesh Prasad, and Johannes B. Goll
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Adult ,Squalene ,0301 basic medicine ,H5N1 vaccine ,medicine.medical_treatment ,alpha-Tocopherol ,Polysorbates ,Adaptive Immunity ,Biology ,Peripheral blood mononuclear cell ,Major Articles and Brief Reports ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Adjuvants, Immunologic ,Double-Blind Method ,Interferon ,Influenza, Human ,Leukocytes ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Innate immune system ,Influenza A Virus, H5N1 Subtype ,Antigen processing ,Gene Expression Profiling ,Acquired immune system ,Immunity, Innate ,Drug Combinations ,030104 developmental biology ,Infectious Diseases ,Influenza Vaccines ,Immunology ,Adjuvant ,Signal Transduction ,medicine.drug - 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.
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- 2018
3. Human Antibody Responses Following Vaccinia Immunization Using Protein Microarrays and Correlation With Cell-Mediated Immunity and Antibody-Dependent Cellular Cytotoxicity Responses
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C. Buddy Creech, Paul Chaplin, Mark J. Mulligan, Wilbur H. Chen, Sharon E. Frey, Thomas M. Kaufman, Lisa A. Jackson, Anna Wald, Samer S. El-Kamary, Jack T. Stapleton, Nadine Rouphael, Travis L. Jensen, Shital M. Patel, Heather Hill, Christine Johnston, Patricia L. Winokur, Hana M. El Sahly, D. Huw Davies, Kathryn M. Edwards, Tammy P Blevins, Zuhair K. Ballas, Wendy L. Rasmussen, Robert B. Belshe, Johannes B. Goll, Srilatha Edupuganti, Robert L. Atmar, Magdalena Tary-Lehmann, and Wendy A. Keitel
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0301 basic medicine ,Modified vaccinia Ankara ,viruses ,Protein Array Analysis ,Vaccinia virus ,Vaccines, Attenuated ,complex mixtures ,03 medical and health sciences ,chemistry.chemical_compound ,Major Articles and Brief Reports ,0302 clinical medicine ,Antigen ,Vaccines, DNA ,Vaccinia ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Antigens, Viral ,Antibody-dependent cell-mediated cytotoxicity ,Immunity, Cellular ,biology ,ELISPOT ,Virion membrane ,Antibody-Dependent Cell Cytotoxicity ,hemic and immune systems ,Viral Vaccines ,Titer ,030104 developmental biology ,Infectious Diseases ,chemistry ,Immunology ,Antibody Formation ,biology.protein ,Immunization ,Antibody ,Smallpox Vaccine - Abstract
Background There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. Methods A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results. Results MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses. Conclusions MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development. Clinical Trials Registration NCT00914732.
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- 2020
4. Policy Recommendations for Optimizing the Infectious Diseases Physician-Scientist Workforce
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Jessica Snowden, Upinder Singh, C. Buddy Creech, Wendy S. Armstrong, Kyle J. Popovich, Jatin M. Vyas, Ebbing Lautenbach, Jaclyn Levy, and Roger Bedimo
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media_common.quotation_subject ,education ,Human immunodeficiency virus (HIV) ,MEDLINE ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Mentorship ,030225 pediatrics ,medicine ,Immunology and Allergy ,Attrition ,030212 general & internal medicine ,book ,health care economics and organizations ,Health policy ,media_common ,Medical education ,medicine.disease ,humanities ,Infectious Diseases ,Workforce ,Pediatric Infectious Disease ,book.journal ,Business ,Diversity (politics) - Abstract
The Infectious Diseases Society of America, HIV Medicine Association, and Pediatric Infectious Diseases Society are concerned by the continued decline in the number of infectious diseases trainees pursuing careers as physician-scientists and the attrition of junior and midcareer physician-scientists. The inability to replace the aging physician-scientist workforce will have a negative, long-lasting impact our biomedical research enterprise and its ability to drive the discovery of new treatments for important infectious diseases. We discuss policy recommendations for securing and optimizing the infectious diseases physician-scientist workforce in the areas of education, training, compensation, and mentorship, as well as ways to improve federal research funding, cross-sector collaboration, and workforce diversity.
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- 2018
5. Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children
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Getahun Abate, Isaac G. Sakala, Steven M. Truscott, Kathryn M. Edwards, Edwin L. Anderson, Robert B. Belshe, Irene Graham, Shewangizaw Worku, Charles T. Spencer, David I. Bernstein, Daniel F. Hoft, Frances K. Newman, Michael A. Gerber, Elizabeth Babusis, C. Buddy Creech, and Kathleen R. Lottenbach
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Male ,Enzyme-Linked Immunospot Assay ,T cell ,T-Lymphocytes ,Immunization, Secondary ,Biology ,Antibodies, Viral ,Vaccines, Attenuated ,Major Articles and Brief Reports ,Immunity ,Influenza, Human ,medicine ,Immunology and Allergy ,Live attenuated influenza vaccine ,Humans ,Heterosubtypic immunity ,Hemagglutination assay ,Vaccination ,Infant ,Hemagglutination Inhibition Tests ,Flow Cytometry ,Virology ,Infectious Diseases ,medicine.anatomical_structure ,Immunization ,Vaccines, Inactivated ,Influenza Vaccines ,Child, Preschool ,Immunology ,biology.protein ,Female ,Antibody ,CD8 - Abstract
Background. Two doses of either trivalent live attenuated or inactivated influenza vaccines (LAIV and TIV, respectively) are approved for young children ($24 months old for LAIV and $6 months old for TIV) and induce protective antibody responses. However, whether combinations of LAIV and TIV are safe and equally immunogenic is unknown. Furthermore, LAIV is more protective than TIV in children for unclear reasons. Methods. Children 6‐35 months old were administered, 1 month apart, 2 doses of either TIV or LAIV, or combinations of LAIV and TIV in both prime/boost sequences. Influenza-specific antibodies were measured by hemagglutination inhibition (HAI), and T cells were studied in flow cytometric and functional assays. Highly conserved M1, M2, and NP peptides predicted to be presented by common HLA class I and II were used to stimulate interferon-c enzyme-linked immunospot responses. Results. All LAIV and/or TIV combinations were well tolerated and induced similar HAI responses. In contrast, only regimens containing LAIV induced influenza-specific CD4 1 , CD8 1 , and cdT cells, including T cells specific for highly conserved influenza peptides. Conclusions. Prime/boost combinations of LAIV and TIV in young children were safe and induced similar protective antibodies. Only LAIV induced CD4 1 ,C D8 1 ,a ndcd T cells relevant for broadly protective heterosubtypic immunity.
- Published
- 2011
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