Hypothesis
An LVS mutant that stimulates human antigen-presenting cells better than wild type would make a better tularemia vaccine, so in vitro screening of antigen-presenting-cell interaction could rationally pre-select candidates before animal work.
What failed
Strain 13B47 raised proinflammatory cytokine secretion from dendritic cells and macrophages, increased costimulatory molecule expression and activated T cells more efficiently than wild-type LVS, and a clean deletion allele reproduced those in vitro properties, yet vaccination with it did not improve survival after challenge with a virulent type A Francisella strain; the mutant was attenuated for growth in vivo and failed to stimulate comparable T cell responses in the lung.
Broken assumption
Better stimulation of antigen-presenting cells in vitro predicts vaccine efficacy in vivo.
Why
The authors conclude that improved antigen-presenting-cell stimulation in vitro did not correlate with protection against challenge in this model system.
From the published paper: Schmitt et al. PLoS ONE, 2012. ↗CC BY