02647nas a2200457   4500000000100000000000100001008004100002260000900043653001300052653002000065653001500085653001500100653001200115100001700127700002000144700001900164700001600183700001500199700001700214700001600231700002000247700001700267700001600284700001700300700002000317700001900337700001800356700001900374700001600393700002300409700001400432700002600446700001800472700002100490245012700511856006700638300001200705490000600717520145200723022001402175       2022                            d  c202210aantibody10agerminal center10alymph node10aorgan chip10avaccine1 aGirija Goyal1 aPranav Prabhala1 aGautam Mahajan1 aBruce Bausk1 aTal Gilboa1 aLiangxia Xie1 aYunhao Zhai1 aRoey Lazarovits1 aAdam Mansour1 aMin Sun Kim1 aAditya Patil1 aDanielle Curran1 aJaclyn M. Long1 aSanjay Sharma1 aAbidemi Junaid1 aLimor Cohen1 aThomas C. Ferrante1 aOren Levy1 aRachelle Prantil-Baun1 aDavid R. Walt1 aDonald E. Ingber00aEctopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202103241  a21032410 v93 aLymphoid 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.  a2198-3844