Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response
| Autor: | Brian D. Aevermann, Casey P. Shannon, Mark Novotny, Rym Ben-Othman, Bing Cai, Yun Zhang, Jamie C. Ye, Michael S. Kobor, Nicole Gladish, Amy Huei-Yi Lee, Travis M. Blimkie, Robert E. Hancock, Alba Llibre, Darragh Duffy, Wayne C. Koff, Manish Sadarangani, Scott J. Tebbutt, Tobias R. Kollmann, Richard H. Scheuermann |
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| Přispěvatelé: | J. Craig Venter Institute [La Jolla, USA] (JCVI), St. Paul’s Hospital - University of British Columbia [Vancouver, BC, Canada], University of British Columbia (UBC), The University of Western Australia (UWA), Simon Fraser University (SFU.ca), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Human Vaccines Project [New York], BC Children's Hospital Research Institute [Vancouver, BC, Canada] (BCCHR), University of California [San Diego] (UC San Diego), University of California, La Jolla Institute for Immunology [La Jolla, CA, États-Unis], This work was supported by the Human Vaccines Project. Additional funding from the Canadian Institutes for Health Research FDN-154287 to RH is gratefully acknowledged. RH holds a Canada Research Chair and a UBC Killam Professorship. DD acknowledges support from the Milieu Interieur Consortium., St. Paul’s Hospital - University of British Columbia [Vancouver, BC, Canada] (SPH-UBC), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), University of California (UC) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Endotype medicine.disease_cause computer.software_genre 0302 clinical medicine baseline correlates Immunology and Allergy Medicine MESH: High-Throughput Nucleotide Sequencing MESH: Hepatitis B Antibodies Original Research canonical correlation analysis MESH: Aged 0303 health sciences MESH: Middle Aged MESH: Machine Learning MESH: Dendritic Cells Vaccination High-Throughput Nucleotide Sequencing Middle Aged vaccines Hepatitis B 3. Good health MESH: Canonical Correlation Analysis machine learning endotypes 030220 oncology & carcinogenesis Host-Pathogen Interactions [SDV.IMM]Life Sciences [q-bio]/Immunology Female Single-Cell Analysis MESH: Vaccine Efficacy Adult Hepatitis B vaccine Immunology Vaccine Efficacy Machine learning 03 medical and health sciences MESH: Gene Expression Profiling Immune system single cell RNA sequencing Humans Hepatitis B Vaccines dendritic cells Hepatitis B Antibodies 030304 developmental biology Aged Hepatitis B virus MESH: Hepatitis B Vaccines Innate immune system MESH: Humans MESH: Hepatitis B business.industry Gene Expression Profiling MESH: Host-Pathogen Interactions MESH: Adult Dendritic cell MESH: Vaccination RC581-607 MESH: Male Immunization Artificial intelligence Immunologic diseases. Allergy business computer MESH: Female MESH: Single-Cell Analysis |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Frontiers, 2021, 12, pp.690470. ⟨10.3389/fimmu.2021.690470⟩ Frontiers in Immunology, 2021, 12, pp.690470. ⟨10.3389/fimmu.2021.690470⟩ Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | International audience; Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype” at pre-vaccination baseline, could dictate response to vaccination. |
| Databáze: | OpenAIRE |
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