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Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response
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....
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588842/ https://www.ncbi.nlm.nih.gov/pubmed/34777332 http://dx.doi.org/10.3389/fimmu.2021.690470 |
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author | Aevermann, Brian D. Shannon, Casey P. Novotny, Mark Ben-Othman, Rym Cai, Bing Zhang, Yun Ye, Jamie C. Kobor, Michael S. Gladish, Nicole Lee, Amy Huei-Yi Blimkie, Travis M. Hancock, Robert E. Llibre, Alba Duffy, Darragh Koff, Wayne C. Sadarangani, Manish Tebbutt, Scott J. Kollmann, Tobias R. Scheuermann, Richard H. |
author_facet | Aevermann, Brian D. Shannon, Casey P. Novotny, Mark Ben-Othman, Rym Cai, Bing Zhang, Yun Ye, Jamie C. Kobor, Michael S. Gladish, Nicole Lee, Amy Huei-Yi Blimkie, Travis M. Hancock, Robert E. Llibre, Alba Duffy, Darragh Koff, Wayne C. Sadarangani, Manish Tebbutt, Scott J. Kollmann, Tobias R. Scheuermann, Richard H. |
author_sort | Aevermann, Brian D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8588842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85888422021-11-13 Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response Aevermann, Brian D. Shannon, Casey P. Novotny, Mark Ben-Othman, Rym Cai, Bing Zhang, Yun Ye, Jamie C. Kobor, Michael S. Gladish, Nicole Lee, Amy Huei-Yi Blimkie, Travis M. Hancock, Robert E. Llibre, Alba Duffy, Darragh Koff, Wayne C. Sadarangani, Manish Tebbutt, Scott J. Kollmann, Tobias R. Scheuermann, Richard H. Front Immunol Immunology 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. Frontiers Media S.A. 2021-10-29 /pmc/articles/PMC8588842/ /pubmed/34777332 http://dx.doi.org/10.3389/fimmu.2021.690470 Text en Copyright © 2021 Aevermann, Shannon, Novotny, Ben-Othman, Cai, Zhang, Ye, Kobor, Gladish, Lee, Blimkie, Hancock, Llibre, Duffy, Koff, Sadarangani, Tebbutt, Kollmann and Scheuermann https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Aevermann, Brian D. Shannon, Casey P. Novotny, Mark Ben-Othman, Rym Cai, Bing Zhang, Yun Ye, Jamie C. Kobor, Michael S. Gladish, Nicole Lee, Amy Huei-Yi Blimkie, Travis M. Hancock, Robert E. Llibre, Alba Duffy, Darragh Koff, Wayne C. Sadarangani, Manish Tebbutt, Scott J. Kollmann, Tobias R. Scheuermann, Richard H. Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response |
title | Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response |
title_full | Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response |
title_fullStr | Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response |
title_full_unstemmed | Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response |
title_short | Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response |
title_sort | machine learning-based single cell and integrative analysis reveals that baseline mdc predisposition correlates with hepatitis b vaccine antibody response |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588842/ https://www.ncbi.nlm.nih.gov/pubmed/34777332 http://dx.doi.org/10.3389/fimmu.2021.690470 |
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