An adjuvant-modulated vaccine response in human whole blood

Abstract

The restimulation of an immune memory response by in vitro culture of blood cells with a specific antigen has been used as a way to gauge immunity to vaccines for decades. In this commentary we discuss a less appreciated application to support vaccine process development. We report that human whole blood from pre-primed subjects can generate a profound adjuvant-modulated, antigen-specific response to several different vaccine formulations. The response is able to differentiate subtle changes in the quality of an immune memory response to vaccine formulations and can be used to select optimal conditions relating to a particular manufacture process step. While questions relating to closeness to in vivo vaccination remain, the approach is another big step nearer to the more relevant human response. It has special importance for new adjuvant development, complementing other preclinical in vivo and in vitro approaches to considerably de-risk progression of novel vaccines before and throughout early clinical development. Broader implications of the approach are discussed.

Keywords: Adjuvant; Human whole blood; Immune response; Memory T cells; Vaccine.

Figure 1.

A comparison of 3 vaccine manufacture process conditions. The diluted fresh hWB from subject S05 was cultured with 3 different H4-IC31 formulations (MPC 1–3) using 30 wells/formulation in a standard 96 U-well microtiter plate. All supernatants were harvested after 10 d culture as previously reported. The H4 (0.1 μg/ml) and IC31 (4.0 nmol KLK) alone controls used 10 wells each. The graph shows a scatter plot +/− SD of the IFNγ released by individual wells to highlight differences in the overall quality of the response to each formulation. The MPC 3 formulation yielded significantly lower levels of IFNγ than the MPC 2 formulation (p = 0.013) (Mann Whitney U test).