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.