Cell Reports (Sep 2024)
Acute and persistent responses after H5N1 vaccination in humans
- Richard Apps,
- Angélique Biancotto,
- Julián Candia,
- Yuri Kotliarov,
- Shira Perl,
- Foo Cheung,
- Rohit Farmer,
- Matthew P. Mulè,
- Nicholas Rachmaninoff,
- Jinguo Chen,
- Andrew J. Martins,
- Rongye Shi,
- Huizhi Zhou,
- Neha Bansal,
- Paula Schum,
- Matthew J. Olnes,
- Pedro Milanez-Almeida,
- Kyu Lee Han,
- Brian Sellers,
- Mario Cortese,
- Thomas Hagan,
- Nadine Rouphael,
- Bali Pulendran,
- Lisa King,
- Jody Manischewitz,
- Surender Khurana,
- Hana Golding,
- Robbert G. van der Most,
- Howard B. Dickler,
- Ronald N. Germain,
- Pamela L. Schwartzberg,
- John S. Tsang
Affiliations
- Richard Apps
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Angélique Biancotto
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Julián Candia
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Yuri Kotliarov
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA; Biometric Research Program, Division of Cancer Treatment and Diagnosis, NCI, NIH, Rockville, MD, USA
- Shira Perl
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Foo Cheung
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Rohit Farmer
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Matthew P. Mulè
- Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; NIH Oxford-Cambridge Scholars Program, Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, UCB2 0QQ Cambridge, UK
- Nicholas Rachmaninoff
- Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
- Jinguo Chen
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Andrew J. Martins
- Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
- Rongye Shi
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Huizhi Zhou
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Neha Bansal
- Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
- Paula Schum
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Matthew J. Olnes
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Pedro Milanez-Almeida
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Kyu Lee Han
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Brian Sellers
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Mario Cortese
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA
- Thomas Hagan
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA
- Nadine Rouphael
- Hope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA
- Bali Pulendran
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA; Hope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA
- Lisa King
- Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20993 USA
- Jody Manischewitz
- Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20993 USA
- Surender Khurana
- Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20993 USA
- Hana Golding
- Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20993 USA
- Robbert G. van der Most
- GSK, Rixensart, Belgium
- Howard B. Dickler
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA
- Ronald N. Germain
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA; Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
- Pamela L. Schwartzberg
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA; Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
- John S. Tsang
- NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA; Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Center for Systems and Engineering Immunology, Departments of Immunobiology and Biomedical Engineering, Yale University, New Haven, CT 06520, USA; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 9
p. 114706
Abstract
Summary: To gain insight into how an adjuvant impacts vaccination responses, we use systems immunology to study human H5N1 influenza vaccination with or without the adjuvant AS03, longitudinally assessing 14 time points including multiple time points within the first day after prime and boost. We develop an unsupervised computational framework to discover high-dimensional response patterns, which uncover adjuvant- and immunogenicity-associated early response dynamics, including some that differ post prime versus boost. With or without adjuvant, some vaccine-induced transcriptional patterns persist to at least 100 days after initial vaccination. Single-cell profiling of surface proteins, transcriptomes, and chromatin accessibility implicates transcription factors in the erythroblast-transformation-specific (ETS) family as shaping these long-lasting signatures, primarily in classical monocytes but also in CD8+ naive-like T cells. These cell-type-specific signatures are elevated at baseline in high-antibody responders in an independent vaccination cohort, suggesting that antigen-agnostic baseline immune states can be modulated by vaccine antigens alone to enhance future responses.
