Journal article
Microphysiologic Human Tissue Constructs Reproduce Autologous Age-Specific BCG and HBV Primary Immunization in vitro
Boston Children's Hospital1
Harvard University2
Adaptive Biotechnologies3
Adaptive Immunology, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark4
Department of Biotechnology and Biomedicine, Technical University of Denmark5
Adaptive Immunology, Division of Immunology & Vaccinology, National Veterinary Institute, Technical University of Denmark6
National Veterinary Institute, Technical University of Denmark7
Statens Serum Institut8
Current vaccine development disregards human immune ontogeny, relying on animal models to select vaccine candidates targeting human infants, who are at greatest risk of infection worldwide, and receive the largest number of vaccines. To help accelerate and de-risk development of early-life effective immunization, we engineered a human age-specific microphysiologic vascular-interstitial interphase, suitable for pre-clinical modeling of distinct age-targeted immunity in vitro.
Our Tissue Constructs (TCs) enable autonomous extravasation of monocytes that undergo rapid self-directed differentiation into migratory Dendritic Cells (DCs) in response to adjuvants and licensed vaccines such as Bacille Calmette-Guerin (BCG) or Hepatitis B virus Vaccine (HBV). TCs contain a confluent human endothelium grown atop a tri-dimensional human extracellular matrix substrate, employ human age-specific monocytes and autologous non heat-treated plasma, and avoid the use of xenogenic materials and exogenous cytokines.
Vaccine-pulsed TCs autonomously generated DCs that induced single-antigen recall responses from autologous naive and memory CD4+ T lymphocytes, matching study participant immune-status, including BCG responses paralleling donor PPD status, BCG-induced adenosine deaminase (ADA) activity paralleling infant cohorts in vivo, and multi-dose HBV antigen-specific responses as demonstrated by lymphoproliferation and TCR sequencing.
Overall, our microphysiologic culture method reproduced age- and antigen-specific recall responses to BCG and HBV immunization, closely resembling those observed after a birth immunization of human cohorts in vivo, offering for the first time a new approach to early pre-clinical selection of effective age-targeted vaccine candidates.
Language: | English |
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Publisher: | Frontiers Media S.A. |
Year: | 2018 |
Pages: | 2634 |
ISSN: | 16643224 |
Types: | Journal article |
DOI: | 10.3389/fimmu.2018.02634 |
ORCIDs: | Jensen, Kristoffer J. |
Autologous Immunization Microphysiology Model Newborn SDG 3 - Good Health and Well-being Tissue engineering Vaccine
Adjuvants, Immunologic Adult Aging BCG Vaccine CD4-Positive T-Lymphocytes Dendritic Cells Female Hepatitis B Vaccines Humans Immunologic Memory Immunologic diseases. Allergy Infant, Newborn Male Middle Aged Monocytes RC581-607 Tissue Culture Techniques autologous immunization microphysiology model newborn tissue engineering vaccine