TY - JOUR
KW - antibody
KW - germinal center
KW - lymph node
KW - organ chip
KW - vaccine
AU - Girija Goyal
AU - Pranav Prabhala
AU - Gautam Mahajan
AU - Bruce Bausk
AU - Tal Gilboa
AU - Liangxia Xie
AU - Yunhao Zhai
AU - Roey Lazarovits
AU - Adam Mansour
AU - Min Sun Kim
AU - Aditya Patil
AU - Danielle Curran
AU - Jaclyn M. Long
AU - Sanjay Sharma
AU - Abidemi Junaid
AU - Limor Cohen
AU - Thomas C. Ferrante
AU - Oren Levy
AU - Rachelle Prantil-Baun
AU - David R. Walt
AU - Donald E. Ingber
AB - 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.
BT - Advanced Science
DA - 2022
DO - 10.1002/advs.202103241
IS - 14
LA - en
N2 - 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.
PY - 2022
EP - 2103241
T2 - Advanced Science
TI - Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202103241
VL - 9
Y2 - 2022-05-27
SN - 2198-3844
ER -