Elevated threat and inflammatory signaling have been associated with altered cortical excitability, febrile seizures, neonatal encephalopathy, cardiorespiratory instability, and adverse developmental outcomes. Vaccines Are One Potential Input Into a Larger SystemVaccines are designed to stimulate immune recognition, so some inflammatory signaling is expected. The critical analysis would test interactions:baseline susceptibility × existing threat load × vaccine exposure × immune-inflammatory and metabolic-endocrine response × cortical response × resolution time × developmental trajectory. Vaccination can generate threat signaling and therefore belongs among the biological exposures considered when studying total immunologic-inflammatory or threat load. The scientifically defensible conclusion is therefore neither “vaccines cause autism” nor “every conceivable contribution of vaccination to autism has already been disproved.”