Inadequate sleep associated with lower vaccine-induced humoral immunity

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Mar 19 2023

In a recent study published in Cell Biology, researchers perform a meta-analysis to assess the association between the duration of sleep and humoral responses to vaccination.

Study: A meta-analysis of the associations between insufficient sleep duration and antibody response to vaccination. Image Credit: fizkes / Shutterstock.com

Background

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused unprecedented mortality and morbidity across the globe. Vaccines continue to be the most effective option to mitigate the coronavirus disease 2019 (COVID-19) pandemic; however, simple behavioral interventions that may boost vaccine-induced humoral responses, such as increasing sleep duration, have not been identified.

The National Sleep Foundation recommends seven to nine hours of sleep for healthy adults and seven to eight hours each day for adults over the age of 65 . The immune protection provided by vaccines is dependent on the extent of immunological responses by vaccines. Antibody titers are significant biomarkers of immune protection and can indicate immunity at the initial stages.

Humoral responses vary by sex, age, body mass index (BMI), smoking habits, and comorbidities. The lowest vaccine-induced humoral immunity levels have been reported among older, obese, and hypertensive male smokers.

Notably, one previous study reported that anti-influenza virus immunoglobulin (IgG) titers 10 days following influenza vaccination were more than 50% lower among sleep-deprived individuals.

About the study

In the present study, researchers investigate the impact of inadequate nocturnal sleep in the days surrounding vaccination on vaccine-induced humoral immunity.

The analyses included data on the associations between sleep duration and humoral responses to hepatitis and influenza vaccines. In total, 165 studies were obtained from the PubMed database until July 19, 2022, including search terms such as ‘sleep’ and ‘vaccine.’ In addition, two records were obtained from the list of references, with one record obtained from another data source.  

Only original and peer-reviewed studies published in French or English that were performed on human adult individuals over 19 years of age and assessed objective and/or subjective sleep durations were included in the analysis.

Of the records, 149 were excluded. Taken together, the entire text of 19 studies was reviewed, following which, 12 records were excluded.

Reasons for exclusion included the lack of evaluations of nocturnal sleep durations or humoral responses to vaccines (five studies), duplicate findings in two studies, not evaluating sleep in the days surrounding the vaccination in three studies, and the inclusion of individuals with over 7.5 hours of nocturnal sleep in one study.

One study was also excluded because it measured antibody titers one week to five months following COVID-19 vaccination, which was contrary to other studies with fixed periods for assessment following vaccination.

Data were obtained on the first author’s name, study title, publication year, sample size, sex and age of study participants, and study design. The researchers also reported the different techniques used for evaluating the duration of sleep, of which included single survey items, validated questionnaires, sleep diaries, polysomnography, or actigraphy. The different approaches used for manipulating experimental sleep durations, as well as vaccine-induced humoral responses following vaccination, were also recorded.

The quality of evidence was assessed using the Downs and Black quality index scoring method. Effect size (ES) estimates were determined, with ES estimates ranging between 0.5 and 0.8 considered medium. In addition, an exploratory analysis was performed excluding individuals aged 65 years and older.

Results

Three prospective cohort studies and four experimental studies were considered for the meta-analysis. Inadequate sleep, which was defined as less than six hours per night, around vaccination reduced humoral responses to vaccines; however, these findings were not statistically significant.

After excluding adults over the age of 60, among 299 individuals, the association was significant, with an ES of 0.6. The reduction in humoral responses was comparable to the waning of vaccine-induced antibodies within two months of vaccination with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine.

This association appeared to be robust for males but not for females, with ES values of 0.8 and 0.6, respectively. This difference is likely due to the varying sex hormone levels by menstrual cycle phases, hormonal contraception use, the status of menopause, and using hormonal replacement therapies among post-menopausal females.  

Objectively assessed short sleep was associated with a robust decrease in antibody responses. Pooled ES estimates for experimental studies (n=133) and prospective studies (n=171) were 0.9 and 0.7, respectively. Pooled ES estimates for men and women were 0.9 and 0.4, respectively.

These findings indicate that self-documented and objective sleep are moderately correlated and that subjective reports tend to overestimate actual sleep duration.

Conclusions

The current study demonstrated that optimizing the duration of sleep around the time of vaccination might boost vaccine-induced humoral immunity. This is a relatively easy, efficient, acceptable, and feasible behavioral modification that can be used to optimize humoral responses to vaccination.

However, large trials that control for known hormonal modulators of immunological function are needed to determine the optimal timing of sleep duration for maximal immune benefit, elucidate the reasons for the sexual disparity in the impact of sleep on immunity, and determine the sleep duration required for protecting the humoral responses.