In vitro antibody response to tetanus in the MIMIC system is a representative measure of vaccine immunogenicity.
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.
Byers
Anthony M
AM
VaxDesign Corporation, Orlando, FL 32826, USA. tbyers@vaxdesign.com
Tapia
Tenekua M
TM
Sassano
Emily R
ER
Wittman
Vaughan
V
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
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines