BETHESDA, MD — Noting that vaccine immunogenicity is affected by a variety of factors, melatonin has been reported to affect immune responses to vaccines and infection, according to a new study.
Researchers from Walter Reed National Military Medical Center and colleagues conducted a randomized open-label trial in which adults scheduled to receive the influenza vaccine were randomized to 5 mg melatonin or control to evaluate the effect of post-vaccination melatonin on humoral (hemagglutination-inhibition assays, HAI) and cellular (FluoroSpot) vaccine-specific cytokine responses 14-21 days post-vaccination. The Uniformed Services University of the Health Sciences, the Henry M. Jackson Foundation for the Advancement of Military Medicine, all in Bethesda; the Naval Medical Research Command in Silver Spring, MD, and General Dynamics Information Technology in Falls Church, VA, also participated in the study.
The study was completed by 108 participants—53 in the melatonin treatment group and 55 in the control group. The groups were similar in baseline characteristics, including sleep as measured by the Pittsburgh Sleep Quality Index. Results published in Human Vaccines & Immunotherapeutics indicated that seroconversion rates or geometric mean fold rises (GMFR) in HAI titers did not vary by treatment group. The study team also found no statistically significant differences between pre- and post-vaccination levels of interferon gamma (IFN-γ) or granzyme B (GzB) by treatment.1
On the other hand, there was a significantly higher fold rise in the double secretor (IFN-γ + GzB) peripheral blood mononuclear cells for influenza vaccine in subjects taking daily melatonin (GMFR 1.7; 95% CI 1.3, 2.3) compared to those who did not (GMFR 0.9; 95% CI 0.7, 1.1) (p < 0.001). “Daily melatonin for 14 days post-influenza vaccination significantly increased the cellular co-expression of IFN-γ + GzB; however, there were no other differences in the cellular or humoral responses,” the researchers pointed out. “Future studies of the potential utility of melatonin for enhancing vaccine response with larger sample sizes may help elucidate candidate mechanisms for these limited effects, including any interactions with the circadian system.”
- Lee RU, Watson NL, Glickman GL, White L, Isidean SD, Porter CK, Hollis-Perry M, Walther SR, Maiolatesi S, Sedegah M, Ganeshan H, Huang J, Boulifard DA, Ewing D, Sundaram AK, Harrison EM, DeTizio K, Belmonte M, Belmonte A, Inoue S, Easterling A, Cooper ES, Danko J. A randomized clinical trial of the impact of melatonin on influenza vaccine: Outcomes from the melatonin and vaccine response immunity and chronobiology study (MAVRICS). Hum Vaccin Immunother. 2024 Dec 31;20(1):2419742. doi: 10.1080/21645515.2024.2419742. Epub 2024 Nov 13. PMID: 39539030; PMCID: PMC11572083
