Diurnal rhythms in varicella vaccine effectiveness
Dana Danino1,2, Yoav Kalron1, Jeffrey A Haspel3
1Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel.
Insights
Vaccine effectiveness for varicella (chickenpox) varies by administration time. Late morning to afternoon vaccination showed the lowest infection rates, while evening vaccination showed the highest, suggesting a diurnal rhythm in immune response.
Area of Science:
- Immunology
- Vaccinology
- Chronobiology
Background:
- Circadian rhythms significantly influence immune system function.
- Understanding the impact of vaccination timing on immune response is crucial for optimizing vaccine effectiveness.
Purpose of the Study:
- To investigate the association between the time of day of varicella vaccine administration and its effectiveness in young children.
- To determine if circadian rhythms play a role in varicella vaccine efficacy.
Main Methods:
- A national cohort study of 251,141 children under 6 years old vaccinated between 2002 and 2023.
- Vaccination times were categorized into morning, late morning to afternoon, and evening.
- Cox proportional hazards regression was used to analyze breakthrough varicella infections, adjusting for covariates.
Main Results:
- Breakthrough varicella infections occurred in 1.8% of vaccinated children.
- Vaccination during late morning to afternoon (11:00-15:59) was associated with the lowest infection rates (HR 0.88).
- Evening vaccination (16:00-19:59) showed the highest infection rates (HR 1.41), with a significant diurnal pattern observed.
Conclusions:
- The time of day for varicella vaccination significantly impacts its clinical effectiveness.
- Findings support a diurnal rhythm in vaccine effectiveness, similar to observations with COVID-19 vaccines.
- Optimizing vaccination schedules based on diurnal immune patterns may enhance public health outcomes.
Abstract:
BACKGROUNDImmune processes are influenced by circadian rhythms. We evaluate the association between varicella vaccine administration time of day and vaccine effectiveness.METHODSA national cohort, children younger than 6 years, were enrolled between January 2002 and December 2023. We compared children vaccinated during morning (7:00-10:59), late morning to afternoon (11:00-15:59), or evening hours (16:00-19:59). A Cox proportional hazards regression model was used to adjust for ethnicity, sex, and comorbidities. The first varicella infection occurring at least 14 days after vaccination and a second dose administration were treated as terminal events.RESULTSOf 251,141 vaccinated children, 4,501 (1.8%) experienced breakthrough infections. Infection rates differed based on vaccination time, with the lowest rates associated with late morning to afternoon (11:00-15:59), HR 0.88, 95% CI 0.82-0.95, P < 0.001, and the highest rates with evening vaccination (16:00-19:59), HR 1.41, 95% CI 1.32-1.52, P < 0.001. Vaccination timing remained significant after adjustment for ethnicity, sex, and comorbidities. The association between immunization time and infection risk followed a sinusoidal pattern, consistent with a diurnal rhythm in vaccine effectiveness.CONCLUSIONWe report a significant association between the time of varicella vaccination and its clinical effectiveness. Similar association was observed with the COVID-19 vaccine, providing proof of concept consistent with a diurnal rhythm in vaccine effectiveness.
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