Psychological Stress and Antibody Response to Influenza Vaccination: When Is the Critical Period for Stress, and How Does It Get Inside the Body?

Objectives: This study attempted to determine whether stress of moderate intensity could modulate the antibody response to an influenza vaccination in healthy young adults, identify critical periods during which stress could influence antibody response, and delineate behavioral and biological pathways that might explain relations between stress and antibody. Methods: A cohort of 83 healthy young adults underwent 13 days of ambulatory monitoring before, during, and after vaccination. Four times daily, subjects reported the extent to which they felt stressed and overwhelmed and collected a saliva sample that was later used to measure cortisol. A battery of health practices (cigarette smoking, alcohol use, physical activity, sleep hygiene) was assessed daily. Antibody titers to the vaccine components were measured at baseline and at 1-month and 4-month follow-up assessments. Results and Conclusions: To the extent that they reported higher levels of stress across the monitoring period, subjects exhibited poorer antibody responses to the New Caledonia strain of the vaccine. Stress ratings on the 2 days before the vaccine and the day it was given were not associated with antibody response. However, the 10 days afterward appeared to be a window of opportunity during which stress could shape the long-term antibody response to varying degrees. With respect to potential mediating pathways, little evidence emerged in favor of cortisol secretion, alcohol consumption, physical activity, or cigarette smoking. However, analyses were consistent with a pattern in which feelings of stress and loss of sleep become locked into a feed-forward circuit that ultimately diminishes the humoral immune response. These findings may shed light on the mechanisms through which stress increase vulnerability to infectious disease.