One Sentence Summary:The Yellow Fever vaccine induces a CD8 T stem cell-like memory subset that preserves a high degree of "Naïveness" and is stably maintained for over two decades in humans. with no studies beyond five years post-vaccination. 7Hereby, we investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-8 specific CD8 T cells were readily detected in almost all donors (38/41), with frequencies 9 decreasing with time. As previously described, effector cells dominated the response early 10 after vaccination. We detected a population of Naïve-like YF-specific CD8 T cells that was 11 stably maintained for over 25 years and was capable of self-renewal ex vivo. In-depth 12 analyses of markers and genome-wide mRNA profiling showed that Naïve-like YF-specific 13 CD8 T cells in vaccinees: i) were distinct from genuine Naïve cells in unvaccinated donors 14 ii) resembled the recently described stem cell-like memory subset (Tscm), and iii) amongst 15 all differentiated subsets, had profiles closest to the Naïve. Our findings reveal that CD8 16 Tscm are efficiently induced by a vaccine in humans, persist for decades and preserve a 17 particularly high degree of "Naïveness". This supports YF vaccination as an optimal 18 mechanistic model for the study of long-lasting memory CD8 T cells in humans.

The true benefit of iron supplementation for nonanemic menstruating women with fatigue is unknown. We studied the effect of oral iron therapy on fatigue and quality of life, as well as on hemoglobin, ferritin and soluble transferrin receptor levels, in nonanemic iron-deficient women with unexplained fatigue

BackgroundIron deficiency without anemia is related to adverse symptoms that can be relieved by supplementation. Since a blood donation can induce such an iron deficiency, we investigated the clinical impact of iron treatment after a blood donation.MethodsOne week after donation, we randomly assigned 154 female donors with iron deficiency without anemia, aged below 50 years, to a four-week oral treatment of ferrous sulfate versus a placebo. The main outcome was the change in the level of fatigue before and after the intervention. Aerobic capacity, mood disorder, quality of life, compliance and adverse events were also evaluated. Hemoglobin and ferritin were used as biological markers.ResultsThe effect of the treatment from baseline to four weeks of iron treatment was an increase in hemoglobin and ferritin levels to 5.2 g/L (P < 0.01) and 14.8 ng/mL (P < 0.01), respectively. No significant clinical effect was observed for fatigue (-0.15 points, 95% confidence interval -0.9 points to 0.6 points, P = 0.697) or for other outcomes. Compliance and interruption for side effects was similar in both groups. Additionally, blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces.ConclusionsThese data are valuable as they enable us to conclude that donors with iron deficiency without anemia after a blood donation would not clinically benefit from iron supplementation.Trial RegistrationClinicalTrials.gov: NCT00981877