title: In vitro antibody response to tetanus in the MIMIC system is a representative measure of vaccine immunogenicity.
abstract: In response to the recurrent failure of animal vaccine protection studies to accurately predict human trial results, we have developed a fully human modular immune in vitroconstruct (MIMIC) to serve as a preliminary screen for efficacy testing of potential vaccine formulations. To validate the potential of this approach, we monitored the in vitro-generated tetanus (TT)-specific antibody levels in a cohort of donors before and after receiving tetanus vaccination. Purified CD4_T cell and B cell populations were combined with autologous tetanus vaccine-pulsed dendritic cells to generate specific antibody. Enumeration of TT-specific IgG antibody-secreting cells by ELISPOT displayed a significant increase in the magnitude of this population after vaccination. The relative magnitudes of the in vitro-generated TT-specific antibody response before and after vaccination largely recapitulated the TT-specific IgG serum titer profiles measured in the same individuals. These findings provide evidence that the MIMIC system can be a rapid and representative in vitro method for measuring vaccine immunogenicity via induction of the memory B cell response.
authors.affiliation: VaxDesign Corporation, Orlando, FL 32826, USA. tbyers@vaxdesign.com
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Byers
authors.forename: Tenekua M
authors.initials: TM
authors.lastname: Tapia
authors.forename: Emily R
authors.initials: ER
authors.lastname: Sassano
authors.forename: Vaughan
authors.initials: V
authors.lastname: Wittman
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003017:Clostridium tetani / Q000276:immunology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines