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Lack of Sleep May Compromise Hepatitis B Vaccine Response

People who got less than 6 hours of sleep per night showed significantly reduced antibody responses after hepatitis B virus (HBV) vaccination, a finding that may shed light on the well-known association between poor sleep and increased susceptibility to infectious disease, researchers reported in the August 1, 2012, issue of Sleep.

Numerous studies -- as well as anecdote and folk wisdom -- point to a link between lack of sleep and higher likelihood of succumbing to flu and other types of infection. But the mechanisms underlying these associations are not well understood.

Aric Prather from the University of California at San Francisco and colleagues conducted an observational study to determine whether sleep duration, efficiency, and quality -- as assessed in the natural environment rather than in laboratory studies of sleep deprivation -- could predict the magnitude or strength of antibody responses to a novel antigen, in this case HBV, in a group of middle-aged volunteers.

The analysis included 125 healthy adults (70 women, 55 men) in Western Pennsylvania, aged 40 to 60 years. All were non-smokers and they had no history of heart attacks, asthma, recent cancer treatment, psychiatric illness, or diseases that affect the immune system. Further, they were not taking any medications known to affect the nervous, endocrine, or immune systems, they were no more than 30% overweight, and women were not pregnant or breast-feeding. People who showed serological evidence of prior HBV exposure were excluded.

All participants received the standard 3-dose Engerix-B hepatitis B vaccination series. The second injection was given 1 month after the first, and the third dose followed at 6 months. Viral antibody titers were measured prior to the second and third doses to assess primary and secondary antibody responses, and clinical protection was assessed 6 months after the final dose (defined as hepatitis B surface antibody level < 10 mIU/mL).

The researchers used actigraphy (a non-invasive method of monitoring activity and rest cycles) and participants' electronic sleep diaries to assess sleep duration, sleep efficiency (how much time in bed is spent asleep), and self-reported sleep quality.

Results

• Shorter sleep duration, according to actigraphy averaged over 6 consecutive days, was associated with significantly lower secondary antibody response.
• This reduced response was independent of age, sex, body mass index, or response to the initial vaccine dose.
• Shorter sleep duration, according to either actigraphy or sleep diaries, also predicted a decreased likelihood of being clinically protected against hepatitis B at the end of the vaccination series.
• 6 to 7 hours of sleep appeared to be the cut-off for poorer antibody response, with participants who got less than 6 hours per night being nearly 12-fold more likely to remain unprotected than those who slept more than 7 hours.
• However, neither sleep efficiency nor subjective reports of sleep quality were significant predictors of HBV antibody response.
• Psychological stress, as assessed via electronic diaries, was unrelated to antibody levels or likelihood of clinical protection 6 months after finishing the vaccine series.

Based on these findings, the study authors concluded, "Short sleep duration in the natural environment may negatively affect in vivo antibody responses to novel antigens, providing a possible explanation for observed associations of poor sleep with increased susceptibility to infectious disease."

"These findings provide initial evidence that natural variation in sleep may contribute to clinically relevant differences in the magnitude of immune responses to vaccination, possibly providing a physiologic basis for observed differences in susceptibility to infection," they elaborated in their discussion. "Indeed, the magnitude of the sleep effect observed in this study is comparable to other known risk factors (age, sex, BMI, smoking status) for clinical non-protection after the hepatitis B vaccination series."

With regard to the biological mechanisms involved, they noted that prolonged sleep deprivation has been associated with shifts in numbers of T-cells and B-cells in peripheral circulation, diminished antigen-specific T-helper cell responses, decline in production of cytokines that play a role in immune response, and increased levels of systemic inflammation. Sleep-related changes in neuroendocrine function also likely play a role.

"Observed associations of shorter sleep duration with lower antibody responses to vaccination and decreased likelihood of mounting a clinically protective response raises the possibility that interventions designed to promote sleep may be of health benefit," they wrote. "However, given the preliminary nature of this work, further exploration of sleep-immune relationships is needed because it may assist in the development of novel therapeutic strategies, including potential sleep interventions to modify infectious disease risk."

8/14/12

Reference

AA Prather, M Hall, JM Fury, et al. Sleep and antibody response to hepatitis B vaccination. Sleep 35(8):1063-1069. August 1, 2012.