Clinical Trial in a Test Tube™ for Influenza Vaccines

VaxDesign successfully predicted the response of donors based on the levels of antibodies that neutralize or clear the virus. In this experiment, we created MIMIC® models using white blood cells taken from donors both before and after seasonal influenza vaccination. Thus, each donor served as his or her own control. We found that the MIMIC® responses and human responses (as measured by serum antibody levels) correlated extremely well.

This study used seasonal inactivated trivalent influenza vaccine in eighteen (18) donors. The donors were pre-bled prior to receiving the 2007-2008 vaccine. Donors were then vaccinated and subsequently bled. Donor serum was tested for influenza specific responses using ELISA, both pre-vaccination and post-vaccination. Donor immune cells were placed into the MIMIC® System both pre-vaccination and post-vaccination, with influenza specific antibody responses measured by ELISA.

As illustrated below, MIMIC® results demonstrated a highly significant elevation in influenza specific responses in both pre-vaccination and post-vaccination samples. We also noted a significant increase in anti-influenza antibody (IgG) in the post-vaccination samples where a similar profile of response was recorded in serological analysis. This observation demonstrates a good correlation between the MIMIC® System and human serology. In the chart on the right, in vitro MIMIC® System is the first set of light and dark blue bars; in vivo vaccination is the second set of light and dark green bars.

This is a particularly interesting observation because serology measures the presence of soluble immunoglobulin in the circulation, whereas the MIMIC® System response is dependent upon the frequency of antigen specific cells in the periphery (which populate the MIMIC® System and ultimately mature and produce antigen specific immunoglobulin). Evaluation of either or both of these components of humoral immunity is indicative of the efficacy of a vaccine. We also noted that the HAI titers increased for both the MIMIC® and sera samples following vaccination with the seasonal influenza vaccination.

The MIMIC® System is capable of demonstrating the effect of vaccination “boosting”. The antibody titers were higher in the MIMIC® System when using PBMCs from donors that had already been vaccinated in vivo (compare pre and post gray bars on left figure).

Donors were vaccinated in vivo with seasonal influenza – green bars. PBMCs from donors (pre and post in vivo vaccination) were also in vitro vaccinated with the seasonal influenza vaccine (left figure, gray bars).