TY - JOUR
KW - Adaptive immunity
KW - Germinal centres
KW - Immunological techniques
KW - vaccines
AU - Lisa E. Wagar
AU - Ameen Salahudeen
AU - Christian M. Constantz
AU - Ben S. Wendel
AU - Michael M. Lyons
AU - Vamsee Mallajosyula
AU - Lauren P. Jatt
AU - Julia Z. Adamska
AU - Lisa K. Blum
AU - Neha Gupta
AU - Katherine J. L. Jackson
AU - Fan Yang
AU - Katharina Röltgen
AU - Krishna M. Roskin
AU - Kelly M. Blaine
AU - Kara D. Meister
AU - Iram N. Ahmad
AU - Mario Cortese
AU - Emery G. Dora
AU - Sean N. Tucker
AU - Anne I. Sperling
AU - Aarti Jain
AU - D. Huw Davies
AU - Philip L. Felgner
AU - Gregory B. Hammer
AU - Peter S. Kim
AU - William H. Robinson
AU - Scott D. Boyd
AU - Calvin J. Kuo
AU - Mark M. Davis
AB - Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.
BT - Nature Medicine
DA - 2021-01
DO - 10.1038/s41591-020-01145-0
IS - 1
LA - en
N2 - Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.
PY - 2021
SP - 125
EP - 135
T2 - Nature Medicine
TI - Modeling human adaptive immune responses with tonsil organoids
UR - https://www.nature.com/articles/s41591-020-01145-0
VL - 27
Y2 - 2023-08-09
SN - 1546-170X
ER -