Clinical Trial in a Test Tube™ for Influenza Vaccines

The VaxDesign Campus of Sanofi Pasteur 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).

Chart comparing Flu-specific antibody production of MIMIC System to Serum

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).