We aimed to synthesize and critically evaluate human studies on the impact of circadian and sleep factors on influenza vaccine-induced immune responses. A comprehensive literature review was conducted, and of the 1260 studies identified, 13 met the inclusion criteria for evaluating vaccination timing, circadian misalignment, and sleep parameters in relation to influenza vaccine-induced immune responses in human populations. Most studies assessed humoral immune responses, primarily antibody titers. Morning vaccination (typically between 9:00 and 11:00 AM) was associated with higher antibody titers compared to afternoon vaccination, particularly for the A/H1N1 strain in adults aged ≥ 65 years. Short sleep duration-especially in the two nights preceding vaccination-was associated with reduced antibody levels, while acute sleep deprivation the night after vaccination transiently reduced antibody levels in males. Sleep fragmentation and excessive daytime sleepiness were linked to increased vulnerability to breakthrough infections. Evidence on circadian misalignment from shift work was mixed. Clinical outcomes were reported in one large trial, where morning vaccination correlated with fewer respiratory hospitalizations. Current evidence supports a potential role for circadian timing and sleep duration in enhancing vaccine-induced antibody responses, particularly in older adults and individuals with sleep or circadian disruption. However, inconsistencies, modest effect sizes, and methodological limitations preclude broad recommendations. Future studies should incorporate direct measures of circadian phase, stratify by chronotype and population (e.g., shift workers), and evaluate both immunologic and clinical outcomes to inform targeted chrono-immunization strategies. Data were extracted on study design and methodology, participant characteristics, vaccine type and administration timing, measured immune outcomes (e.g., antibody titers, T-cell activity) and sleep or circadian-related exposures (e.g., sleep duration, circadian misalignment). Discrepancies between reviewers were resolved through discussion to ensure consensus. Given the heterogeneity of study designs, exposure definitions, populations, and outcome measures, a narrative synthesis approach rather than a meta-analysis was employed. et al., 2025, UK [ 19 ] Pneumococcal IgG/IgA/IgM and influenza HAI titers over 1 year AM (08:00–10:00) vs. PM (16:00–18:00); PPV-23 + quadrivalent influenza Both groups increased pneumococcal and influenza titers; no time-of-day differences in magnitude or durability for any isotype/strain Questionnaire on sleep duration, activity, diet; cortisol/cytokine profiling Null contrasts earlier elderly findings; self-selected slots; younger cohort; co-administration may dilute effect; only two time windows tested IgG/IgA/IgM, immunoglobulin G/A/M. 3.2. In one study, older men with excessive daytime sleepiness had significantly lower antibody titers to the influenza A/H3N2 strain 28 days post-vaccination with a trivalent vaccine compared to those with regular sleep patterns, suggesting even minor sleep disruptions can impair vaccine-induced immune response [ 23 ]. Chronic insomnia has also been associated with diminished humoral responses [ 24 ]. Taylor D.J. et al. reported that patients with chronic insomnia had significantly weaker humoral response four weeks post-influenza vaccination, potentially due to persistently elevated inflammatory markers [ 24 ]. 3.3. Light Exposure and Circadian Stability Münch et al. Mechanistic Basis of Morning Vaccine-Induced Immune Response Circadian regulation of immune function likely explains the enhanced response to morning vaccination. Studies indicate that antigen presentation, T-cell activation, and cytokine release (e.g., IFN-gamma) peak during morning (between 9:00 and 11:00 am), aligning with better immunogenicity [ 12 , 13 , 14 , 15 , 16 , 17 ]. This temporal alignment appears particularly advantageous for influenza vaccines, where rapid activation of both humoral and cellular immunity is crucial for establishing protection against seasonal strains. While similar chronobiological principles may apply to other vaccine platforms, the unique virological characteristics of influenza—including rapid mutation rates and strain-specific antigenic drift—suggest these circadian interactions may be particularly consequential for annual influenza vaccination strategies. 4.2. Sleep Duration, Quality and Continuity Adequate sleep before and shortly after vaccination supports early immune processes such as antigen processing and T-cell priming [ 7 , 29 ]. The transient nature of sleep deprivation effects underscores the importance of timing and duration of sleep rather than chronic effects [ 7 , 29 ]. Together, these observations highlight the need for targeted vaccination approaches in populations experiencing circadian disruption, whether due to aging, occupational demands, or other lifestyle factors. 4.6. Broad Vaccination Insights Emerging evidence from other vaccination studies suggests circadian influences similar to influenza vaccines, with systematic reviews, trials, and observational cohorts demonstrating stronger antibody responses following morning vaccination and adequate peri-vaccination sleep, though effect sizes vary by population and vaccine platform [ 26 , 32 , 33 , 34 , 35 , 36 ]. This included failure to adjust for multiple comparisons between influenza antigens, lack of control for baseline antibody levels, omission of randomization factors (e.g., primary care practice), and relatively small effect sizes with wide inter-individual variability, as reflected in broad confidence intervals. These issues underscore the need for caution when interpreting the reported effects of circadian timing and sleep on immune responses. Concerns raised by Kurupati et al., particularly regarding confounding from blood sample timing, further illustrate the complexities in

Aging reshapes immunity through immunosenescence and inflammaging, increasing susceptibility to infection, exacerbating chronic conditions, and blunting vaccine responses. This review frames "immunofitness" as a practical goal of healthy aging and examines how adult vaccination builds immune resilience. Vaccination strengthens adaptive memory, leverages adjuvants to optimize antigen presentation, and can reprogramme innate cells (trained immunity), yielding heterologous benefits beyond target pathogens. We integrate evidence in older adults for influenza, respiratory syncytial virus, pneumococcal, COVID-19, and recombinant zoster vaccines, including reductions in respiratory events, cardiovascular outcomes, hospitalization, and mortality. We highlight emerging platforms and precision vaccinology to tailor schedules by immune age, comorbidity, and frailty. Integrating routine, age-appropriate vaccination with lifestyle measures is a feasible, high-impact strategy to promote immunofitness.

Aim Sleep and physical activity are two important lifestyle factors that significantly influence overall health and wellbeing. This comprehensive review aims to provide a detailed understanding of the interplay between sleep and physical activity habits. Methods A narrative review was conducted through a comprehensive assessment of primary and secondary sources, incorporating scientific publications from databases such as MedLine, Cochrane, Embase, PsychINFO, and Cinahl. The inclusion criteria focused on studies published between 2000 and 2025, addressing topics such as physical activity, sleep quality, sleep disorders, energy balance, and related health outcomes. Exclusion criteria included gray literature, unpublished studies, books, conference proceedings, and dissertations. Results The results highlight the complex bidirectional relationship between sleep and physical activity. Regular physical activity improves sleep quality and duration, while adequate sleep enhances physical activity performance and recovery. Sleep disorders negatively affect physical activity engagement, but interventions involving exercise demonstrate significant potential in mitigating these effects. Conclusions In conclusion, understanding the multifaceted interactions among sleep, physical activity, and nutrition is crucial for promoting overall health and wellbeing. Future research should leverage advancements in wearable technology, personalized interventions, and precision medicine approaches t Results The results highlight the complex bidirectional relationship between sleep and physical activity. Regular physical activity improves sleep quality and duration, while adequate sleep enhances physical activity performance and recovery. Sleep disorders negatively affect physical activity engagement, but interventions involving exercise demonstrate significant potential in mitigating these effects. Conclusions In conclusion, understanding the multifaceted interactions among sleep, physical activity, and nutrition is crucial for promoting overall health and wellbeing. Meta-analyses and randomized controlled trials consistently indicate improvements in sleep quality, sleep onset latency, and sleep efficiency following regular physical activity, supporting a clinically meaningful relationship. In contrast, evidence linking physical activity to changes in sleep duration is less consistent, with generally small or null effects reported across studies ( 23 , 28 , 30 ). Despite these strengths, several inconsistencies remain in the literature. Future studies should adopt standardized, objective measures of both physical activity and sleep, incorporate sufficiently long follow-up periods, and explicitly account for moderating factors such as baseline sleep status, chronotype, and comorbidities. Addressing these gaps will be essential to advancing personalized, evidence-based exercise prescriptions aimed at optimizing sleep health. 3. The effects of sleep on physical activity performance and recovery Numerous studies Research suggests that individuals who obtain an adequate amount of sleep exhibit enhanced speed, power, accuracy, and reaction time during exercise. Longer sleep durations have been linked to increased endurance, improved muscular strength, and better overall athletic performance ( 137 ). Adequate sleep duration enables the body to replenish energy stores, repair damaged tissues, and optimize neural and physiological processes necessary for optimal physical performance ( 138 ). On the contrary, inadequate sleep duration has been shown to impair physical activity performance ( 139 ). Overall, these findings suggest that time zone change, in any direction, is likely to negatively impact competitive performance, with sleep health being a central factor in these relationships ( 137 ). 7. The potential mechanisms underlying the relationship between sleep and physical activity, including the role of circadian rhythms, hormonal regulation, and neural pathways The mechanisms regulating sleep have an impact on the gene expression of the central nervous system (CNS) and involve the endocrine, immune, and energy regulation systems. Sleep is determined by the activation of the SCN, which integrates information from all parts of the organism ( 151 ). On the contrary, people with low or no physical activity presented less slow brain wave activity in addition to a greater predisposition to present depressive symptomatology. This indicates that these processes are interrelated and that these two systems work together to maintain organic homeostasis ( 164 – 166 ). Sleep is also related to hormonal regulation. In relation to the immune system, proinflammatory cytokines are in charge of modulating sleep and their activity is altered with sleep deprivation ( 69 , 167 ). Individual differences: Investigate individual differences in the relationship between sleep and physical activity. Explore how factors such as age, sex, chronotype, and genetic variations influence the interplay between sleep and physical activity. Technology and interventions: Explore the potential of wearable technology and personalized interventions for monitoring and enhancing sleep and physical activity habits. Investigate the effectiveness of mobile applications, wearable devices, and personalized feedback systems in promoting healthy sleep and physical activity behaviors. 13. Conclusion This narrative review highlights the complex and dynamic bidirectional relationship between sleep and physical activity, emphasizing their joint relevance as modifiable lifestyle behaviors with profound implications for physical, metabolic, and mental health. The evidence consistently indicates that regular physical activity, particularly at moderate intensity, is associated with improvements in sleep quality, while adequate sleep duration and quality are essential for optimizing physical performance, recovery, and long-term engagement in physical activity.