tetano
Editor, Senior Moderator
Adv Sci (Weinh)
. 2022 Mar 14;e2103241.
doi: 10.1002/advs.202103241. Online ahead of print.
Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip
Girija Goyal[SUP] 1 [/SUP], Pranav Prabhala[SUP] 1 [/SUP], Gautam Mahajan[SUP] 1 [/SUP], Bruce Bausk[SUP] 1 2 [/SUP], Tal Gilboa[SUP] 1 2 [/SUP], Liangxia Xie[SUP] 1 2 [/SUP], Yunhao Zhai[SUP] 1 [/SUP], Roey Lazarovits[SUP] 1 [/SUP], Adam Mansour[SUP] 1 [/SUP], Min Sun Kim[SUP] 1 [/SUP], Aditya Patil[SUP] 1 [/SUP], Danielle Curran[SUP] 1 [/SUP], Jaclyn M Long[SUP] 1 [/SUP], Sanjay Sharma[SUP] 1 [/SUP], Abidemi Junaid[SUP] 1 [/SUP], Limor Cohen[SUP] 1 2 [/SUP], Thomas C Ferrante[SUP] 1 [/SUP], Oren Levy[SUP] 1 [/SUP], Rachelle Prantil-Baun[SUP] 1 [/SUP], David R Walt[SUP] 1 2 [/SUP], Donald E Ingber[SUP] 1 3 4 [/SUP]
Affiliations
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.
Keywords: antibody; germinal center; lymph node; organ chip; vaccine.
. 2022 Mar 14;e2103241.
doi: 10.1002/advs.202103241. Online ahead of print.
Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip
Girija Goyal[SUP] 1 [/SUP], Pranav Prabhala[SUP] 1 [/SUP], Gautam Mahajan[SUP] 1 [/SUP], Bruce Bausk[SUP] 1 2 [/SUP], Tal Gilboa[SUP] 1 2 [/SUP], Liangxia Xie[SUP] 1 2 [/SUP], Yunhao Zhai[SUP] 1 [/SUP], Roey Lazarovits[SUP] 1 [/SUP], Adam Mansour[SUP] 1 [/SUP], Min Sun Kim[SUP] 1 [/SUP], Aditya Patil[SUP] 1 [/SUP], Danielle Curran[SUP] 1 [/SUP], Jaclyn M Long[SUP] 1 [/SUP], Sanjay Sharma[SUP] 1 [/SUP], Abidemi Junaid[SUP] 1 [/SUP], Limor Cohen[SUP] 1 2 [/SUP], Thomas C Ferrante[SUP] 1 [/SUP], Oren Levy[SUP] 1 [/SUP], Rachelle Prantil-Baun[SUP] 1 [/SUP], David R Walt[SUP] 1 2 [/SUP], Donald E Ingber[SUP] 1 3 4 [/SUP]
Affiliations
- PMID: 35289122
- DOI: 10.1002/advs.202103241
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.
Keywords: antibody; germinal center; lymph node; organ chip; vaccine.