Acute and persistent responses after H5N1 vaccination in humans
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<sup>+</sup> 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.
Authors
- Robbert van der Most (ORCID: https://orcid.org/0000-0002-3065-6946)
- Matthew P. Mulè (ORCID: https://orcid.org/0000-0001-8457-2716)
- Shira Perl
- Rohit Farmer (ORCID: https://orcid.org/0000-0003-4197-3047)
- Andrew J. Martins (ORCID: https://orcid.org/0000-0002-1832-1924)
- Foo Cheung
- Hana Golding (ORCID: https://orcid.org/0000-0001-8116-694X)
- Howard B. Dickler
- John S. Tsang (ORCID: https://orcid.org/0000-0003-3186-3047)
- Rongye Shi (ORCID: https://orcid.org/0000-0003-4298-9358)
- Brian A. Sellers (ORCID: https://orcid.org/0000-0003-1268-0341)
- Paula Schum
- Bali Pulendran (ORCID: https://orcid.org/0000-0001-6517-4333)
- Nadine Rouphael (ORCID: https://orcid.org/0000-0002-2512-7919)
- Mario Cortese
- Matthew J. Olnes (ORCID: https://orcid.org/0000-0002-7791-5554)
- Jody Manischewitz
- Pedro Milanez‐Almeida (ORCID: https://orcid.org/0000-0001-8285-957X)
- Yuri Kotliarov (ORCID: https://orcid.org/0000-0002-6558-8883)
- Julián Candia (ORCID: https://orcid.org/0000-0001-5793-8989)
- Nicholas Rachmaninoff (ORCID: https://orcid.org/0000-0002-3228-3610)
- Surender Khurana (ORCID: https://orcid.org/0000-0002-0593-7965)
- Pamela L. Schwartzberg (ORCID: https://orcid.org/0000-0001-6318-9187)
- Neha M. Bansal (ORCID: https://orcid.org/0000-0001-7026-3058)
- Thomas Hagan (ORCID: https://orcid.org/0000-0002-5254-5251)
- Ronald N. Germain (ORCID: https://orcid.org/0000-0003-1495-9143)
- Angélique Biancotto (ORCID: https://orcid.org/0000-0003-2271-009X)
- Richard Apps (ORCID: https://orcid.org/0000-0001-5140-0141)
- Jinguo Chen (ORCID: https://orcid.org/0000-0002-8154-0994)
- Huizhi Zhou
- Kyu Lee Han
- Lisa R. King
Institutions
- Center for Biologics Evaluation and Research (US)
- Emory and Henry College (US)
- National Human Genome Research Institute (US)
- GlaxoSmithKline (Belgium) (BE)
- HOPE Clinic (US)
- National Institute of Allergy and Infectious Diseases (US)
- Stanford University (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114706
- Citations
- 11
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 2.65
Funders
- U.S. Department of Health and Human Services
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases