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

doi:10.1016/j.celrep.2024.114706

Acute and persistent responses after H5N1 vaccination in humans

Cell Rep. 2024 Sep 24;43(9):114706. doi: 10.1016/j.celrep.2024.114706. Epub 2024 Sep 4.

Authors

Richard Apps¹, Angélique Biancotto¹, Julián Candia¹, Yuri Kotliarov², Shira Perl¹, Foo Cheung¹, Rohit Farmer¹, Matthew P Mulè³, Nicholas Rachmaninoff⁴, Jinguo Chen¹, Andrew J Martins⁴, Rongye Shi¹, Huizhi Zhou¹, Neha Bansal⁴, Paula Schum¹, Matthew J Olnes¹, Pedro Milanez-Almeida¹, Kyu Lee Han¹, Brian Sellers¹, Mario Cortese⁵, Thomas Hagan⁵, Nadine Rouphael⁶, Bali Pulendran⁷, Lisa King⁸, Jody Manischewitz⁸, Surender Khurana⁸, Hana Golding⁸, Robbert G van der Most⁹, Howard B Dickler¹, Ronald N Germain¹⁰, Pamela L Schwartzberg¹¹, John S Tsang¹²

Affiliations

¹ NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA.
² NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA; Biometric Research Program, Division of Cancer Treatment and Diagnosis, NCI, NIH, Rockville, MD, USA.
³ 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.
⁴ Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
⁵ Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
⁶ Hope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA.
⁷ 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.
⁸ Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20993 USA.
⁹ GSK, Rixensart, Belgium.
¹⁰ 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.
¹¹ 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.
¹² 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. Electronic address: john.tsang@yale.edu.

PMID: 39235945
DOI: 10.1016/j.celrep.2024.114706

Abstract

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.

Keywords: CP: Immunology; CP: Microbiology; adjuvant; antigen-agnostic memory; baseline immune state; immune response dynamics; single cell analysis; systems immunology; trained immunity; vaccine.

MeSH terms

Adjuvants, Immunologic / pharmacology
Adult
CD8-Positive T-Lymphocytes / immunology
Female
Humans
Influenza A Virus, H5N1 Subtype* / immunology
Influenza Vaccines* / immunology
Influenza, Human* / immunology
Influenza, Human* / prevention & control
Male
Transcriptome / genetics
Vaccination*

Substances

Influenza Vaccines
Adjuvants, Immunologic