How Seasonal Rhythms of the Body Clock Influence Vaccine Effectiveness

Many individuals notice fluctuations in their health correlating with seasons. Recent studies reveal that vaccine responses—and, broadly, our physiological characteristics—vary throughout the year.

While humans are not generally categorized as seasonal beings, many plants and animals adhere to biological calendars that dictate behaviors such as flowering, reproduction, migration, and hibernation. Over the last decade, research has unveiled that humans experience subtle seasonal changes in immune activation, hormone levels, and gene expression.

“The most intriguing discovery from this research isn’t just about vaccines, but rather human immune function. It varies by season,” states Kathy Wyse from the University of Edinburgh, who did not participate in the study. “This indicates that humans may possess an inherent seasonal timing mechanism, akin to that observed in animals and birds.”

Research indicates that the response to influenza vaccines adheres to a 24-hour circadian rhythm. Laura Valero Guevara and her team at New York University explored the implications of seasonality on vaccine effectiveness.

The team analyzed data from 96 randomized controlled trials involving approximately 48,000 children vaccinated against 14 infectious diseases, including measles, polio, and chickenpox. These studies, held in various countries at different times of the year, allowed for a comprehensive comparison of seasonal and geographic differences in immunogenicity—the immune response strength provoked by vaccination.

“We indeed observed a seasonal immune response,” Valero-Guevara shared. “What’s particularly exciting is the latitudinal gradient we noticed. In temperate zones, both in the Northern and Southern Hemispheres, stronger immune responses occurred in the winter, likely influenced by seasonal variations in light exposure.”

As proximity to the equator increased, the immune responses appeared to follow a less predictable seasonal pattern. There remained significant annual fluctuations in vaccine reactions within tropical regions; while some vaccines, like rotavirus and polio, showed marked seasonal variations. However, unlike the consistent winter peaks seen in temperate areas, tropical peak responses varied depending on the specific vaccine.

The researchers excluded any children with pre-existing antibodies against the pathogens prior to vaccination, indicating that recent exposure to infections is unlikely to account for these findings.

However, the underlying causes of these variations remain elusive. “Initially, we posited that seasonal circadian rhythms prompted by changes in light exposure drive these variations. This would imply that the amplitude of seasonality should be less pronounced in tropical areas compared to temperate regions,” said Mathieu Domenech de Sel from the Max Planck Institute for Infection Biology in Berlin. “But that’s not what we found, so other factors, or a combination of light exposure and other influences, might be at play.”

Past research has suggested seasonal patterns in immune activity. In 2020, Wyse and her colleagues reported seasonal variations in inflammatory markers, revealing different immune cell types peak at varied times—some in winter, others in spring.

Additionally, Manuel Ilima and his team at the Genome Control Center in Barcelona identified seasonal patterns in gene expression across multiple human tissues, including hormone-regulating areas of the brain and testes, along with numerous immune-related genes. “While we still lack a clear understanding of the mechanisms, the new findings could be tied to our observations,” suggests Iruma.

Weiss posits that humans may possess an inborn seasonal timing system influenced by variations in daylight. “This mechanism is also revered in animals, birds, and fish, even if we haven’t conclusively demonstrated it in humans yet,” he explains.

Thought to be located in the hypothalamus—which houses the suprachiasmatic nucleus that regulates circadian rhythms—this timing system adapts differently in equatorial animals, where day length stability weakens annual cycles, redirecting ecological reliance towards environmental factors like food availability or rainy seasons.

Evidence suggesting seasonal patterns in humans could extend beyond the immune realm. Earlier this year, Timothy Hearn at the University of Cambridge with David Whitmore of University College London reported that births in Britain exhibited a notable seasonal rhythm, peaking during spring throughout much of the 20th century, until a significant change in the 1970s due to widespread contraceptive access.

Professor Hahn emphasizes that dismissing evidence of seasonal biology in humans is becoming increasingly challenging, but disentangling whether these rhythms represent an inherent biological calendar is complex. “The term ‘season’ encompasses a range of interconnected environmental interactions, along with related shifts in disease exposure, diet, activity, sleep, and social behaviors.”

If the seasonal variations identified by Valero-Guevara and her team are validated, it may prompt considerations around optimizing vaccination schedules based on seasonal health patterns.

Nonetheless, Professor Weiss cautions that differences in antibody responses may not directly translate to significant variances in vaccine efficacy, implying that delaying vaccinations for potential immune improvements could pose greater risks. “Postponing vaccination for a month to target winter could be more hazardous than anticipated,” she states. “Current evidence does not substantiate such an approach.”

“Ultimately, time will determine if there are clinical advantages in scheduling vaccinations seasonally,” she adds. “Presently, the evidence is insufficient to support this.”