Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ‐on‐a‐Chip
Abstract
Lymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model of ectopic LF formation will provide a tool to understand LF development and an alternative to non‐human primates for preclinical evaluation of vaccines. Here, it is shown that primary human blood B‐ and T‐lymphocytes autonomously assemble into ectopic LFs when cultured in a 3D extracellular matrix gel within one channel of a two‐channel organ‐on‐a‐chip microfluidic device. Superfusion via a parallel channel separated by a microporous membrane is required for LF formation and prevents lymphocyte autoactivation. These germinal center‐like LFs contain B cells expressing Activation‐Induced Cytidine Deaminase and exhibit plasma cell differentiation upon activation. To explore their utility for seasonal vaccine testing, autologous monocyte‐derived dendritic cells are integrated into LF Chips. The human LF chips demonstrate improved antibody responses to split virion influenza vaccination compared to 2D cultures, which are enhanced by a squalene‐in‐water emulsion adjuvant, and this is accompanied by increases in LF size and number. When inoculated with commercial influenza vaccine, plasma cell formation and production of anti‐hemagglutinin IgG are observed, as well as secretion of cytokines similar to vaccinated humans over clinically relevant timescales.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 14, 2022
- Source ID
- 10.1002/advs.202103241
Entities
People
- Abidemi Junaid
- Adam Mansour
- Aditya Patil
- Bruce Bausk
- Danielle Curran
- David R. Walt
- Donald E. Ingber
- Gautam Mahajan
- Girija Goyal
- Jaclyn M. Long
- Liangxia Xie
- Limor Cohen
- Min Sun Kim
- Oren Levy
- Pranav Prabhala
- Rachelle Prantil‐baun
- Roey Lazarovits
- Sanjay Sharma
- Tal Gilboa
- Thomas C. Ferrante
- Yunhao Zhai
Organizations
- Biomedical Advanced Research and Development Authority
- Defense Advanced Research Projects Agency
- Harvard Medical School
- Harvard University
- National Institutes of Health