Table 2. A Snapshot of the Research in Time of Vaccination.
| Type of vaccine, Year of publication, country | Setting/methods | Main findings | Conclusion | Ref |
| ►Hepatitis A vaccine ►Influenza vaccine 2008, UK |
►Setting: Observational ►Types of vaccine: hepatitis A vaccine (HAVRIX; Glaxo SmithKline) and Influenza vaccine (the trivalent vaccine consisted of three antigens: A/New Caledonia/20/99; A/Panama/2007/99; and B/Shangdong/7/97). ►Types of vaccine administration: intramuscular injection. ►Data from two studies that examined morning versus afternoon vaccination. ►In the first study, 75 university students (34 men; mean age of 22.9 years) were randomly allocated to either a morning (10 a.m. to 12 p.m.; n=39) or early evening (4 p.m. to 6 p.m.; n=36) hepatitis A vaccination session. ►In the second study, influenza vaccine was administered to 89 (38 men) older (aged 65 years or older) community-based adults. Fifty-nine participants vaccinated in the morning between 8 a.m. and 11 a.m., and 30 in the afternoon between 1 p.m. and 4 p.m. Participants vaccinated between 11 a.m. and 1 p.m. were excluded. ►In both studies the anti-HAV and anti-influenza antibody titers were measured approximately 1 month after vaccination. |
►Participants responded with a significant increase in antibody titer
for all four antigens from baseline to 1 month. ►Vaccinated in the morning in men, but not women, mounted antibody response to both HAV and the influenza strains. |
►Diurnal vaccination enhance hormonal immune response following vaccination. | [24] |
| ►Influenza vaccine 2016, UK | ►Setting: cluster-randomized trial ►Types of vaccine: Trivalent Influenza vaccine ►Types of vaccine administration: intramuscular injection. ►A cluster-randomized trial was designed to evaluate morning versus afternoon vaccination (either 9 and 11 am or 3 and 5 pm) among 276 adults (aged 65+ years) following influenza vaccination. ►One month after vaccination, the anti-influenza antibody titers, serum cytokines IL-6 and IL-10 and seven steroids in serum (cortisol, cortisone, corticosterone, 11-deoxycortisol, testosterone, dehydroepiandrosterone (DHEA) and androstenedione) were measured. |
►Greater antibody response was detected in those individuals who
vaccinated in the morning than afternoon vaccination. ►Cytokines and steroid hormones were not related to antibody responses. |
►Morning vaccination in older adults may be beneficial for the influenza antibody response. | [25] |
| ►Influenza vaccine 2017, USA | ►Setting: Observational ►Types of vaccine: Trivalent Influenza vaccine ►Types of vaccine administration: intramuscular injection. ►A 5-year study to assess immune responses to the influenza A in 114 samples from younger (30–40-year-old) and 165 samples from aged (>65-year-old) individuals who vaccinated in the morning versus afternoon. ►Antibody responses, B cell subset distribution in blood and the blood transcriptome were analyzed before and after vaccination. |
►Timing of vaccination did not affect immune response in younger and
aged individuals. ►The time of sample collection effect on the numbers of some of the B cell subsets in blood and global gene expression of whole blood samples. |
►The time of sample collection effect on the results of immunological factors following influenza vaccination. | [26] |
| ►BCG 2020, Western European countries | ►Setting: Interventional and cohort ►Types of vaccine: BCG vaccine ►Types of vaccine administration: Intradermal injection. ►BCG vaccine was administered in at 6 pm and 6:30 pm (n=18; mean age of 25.8 SD=10.7 years; 61% females) compared with 36 age- and sex-matched volunteers with vaccinated between 8 am and 9 am. ►Peripheral blood mononuclear cells (PBMCs) were stimulated with Staphylococcus aureus and Mycobacterium tuberculosis before, as well as 2 weeks and 3 months after BCG vaccination and Cytokine production was measured in response to stimulation. ►Also, an independent cohort of 302 individuals vaccinated between 8 am and 12 pm with BCG in order to assess influence of vaccination time on induction of trained immunity. |
►Morning vaccination elicited a stronger trained immunity and adaptive
immune phenotype compared with evening vaccination (eg, specific
M. tuberculosis IFN-γ responses were significantly
higher in morning-vaccinated individuals 3 months after BCG vaccination
compared with evening vaccination). ►In a large cohort of 302 volunteers, early morning vaccination resulted in a superior cytokine production capacity compared with later morning. |
►BCG vaccination in the morning induces stronger trained immunity and adaptive responses compared with evening vaccination. | [27] |
| ►Hexavalent vaccine 2019, Germany | ►Setting: Randomized Controlled Trial ►Types of vaccine: Hexavalent vaccine ►Types of vaccine administration: Intramuscular injection. ►Twenty-six infants born at 26–30 weeks’ gestation received their first routine hexavalent vaccination in the morning (7 and 10 a.m.) versus evening (7 and 10 p.m.). ►Pulse oximeter saturation, actigraphy, and rectal temperature were obtained for 24 h before and after vaccination. Antibody titers were measured before and 24 h after vaccination to determine inflammatory markers. |
►Antibody titers for Bordetella pertussis were
increased in both groups, but there was no difference in inflammatory
markers 24 h after vaccination. ►Vaccination led to an increase body temperature and cardiorespiratory event rate (CER) in both groups, but there was no significant difference between the morning and evening groups. |
►The study did not identify a difference in CER between morning and evening vaccination. | [28] |
| ►SARS-CoV-2 inactivated vaccine 2021, China | ►Setting: Prospective cohort study ►Types of vaccine: inactivated SARS-CoV-2 vaccine (BBIBP-CorV, Sinopharm, Beijing). ►Types of vaccine administration: Intramuscular injection. ►The dynamics of immune responses were measured among 63 healthcare workers (HCWs) who received inactivated SARS-CoV-2 vaccine in the morning (9 am–11 am, n = 33) or afternoon (15 pm–17 pm, n = 30). |
►Participants vaccinated in the morning showed significantly higher
level of NAbs in the sera as well as stronger B cell and Tfh responses
to the vaccination. ►The percentages of antibody-secreting cells (ASCs) cells, monocytes, and dendritic cells were significantly higher in the morning vaccination group. |
►These data suggest that vaccination in the morning resulted in a stronger immune response to an inactivated SARS-CoV-2 vaccine than in the afternoon. | [29] |
| ►SARS-CoV-2 mRNA (Pfizer) and Adenoviral (AstraZeneca) vaccine 2022, UK | ►Setting: Randomized Controlled Trial ►Types of vaccine: SARS-CoV-2 mRNA (Pfizer) and Adenoviral (AstraZeneca) vaccine ►Types of vaccine administration: Intramuscular injection. ►Anti-Spike antibody levels were investigated in three times of vaccination (Time 1, 7-10:59 h; Time 2, 11-14:59 h; Time 3, 15-21:59 h), two type of vaccines (Pfizer, mRNA bnt162b2 or AstraZeneca, Adenoviral AZD1222), the age groups (16-29, 30-39, 40-49, or 50-74 years), sex, and the number of days post-vaccination. ►The anti-Spike responses were measured during the 2-10 weeks after vaccination. |
►The anti-Spike responses were higher in those who were vaccinated later
in the day (p = 0.013), in those who received the
Pfizer mRNA vaccine (p<0.0001), in younger
participants (p< 0.0001), and in women (p =
0.013). ►A significant association between days post-vaccination and vaccine type (p<0.0001) and age (p=0.032), but not with vaccine time (p=0.238) were observed. ►The results did not show a significant effect of time of day of vaccination (p=.23), day of sample collection (p = 0.097) and two time intervals (before or after 1 pm). ►Analysis of 2784 health care workers revealed a significant effect of the time of vaccination on anti-Spike antibody levels following the administration of two alternative SARS-CoV-2 vaccines (mRNA or Adenovirus based). |
►The results revealed that the magnitude of the anti-Spike antibody response is associated with the multiple variables, including time of day of vaccination, vaccine type, participant age, sex, and days postvaccination. | [30] |
BCG: Bacillus Calmette–Guérin; CER: cardiorespiratory event ratel; HCWs: healthcare workers; Nab: neutralizing antibody; Tfh: follicular helper T; ASC: antibody-secreting cells; PBMCs: Peripheral blood mononuclear cells; TNF-α: tumor necrosis factor α; IL-1β: interleukin 1β; IFN-γ: Interferon gamma; NAbs: neutralizing antibodies; ASCs: antibody-secreting cells