Antibody-mediated responses play a critical role in vaccine-mediated immunity. However, for reasons that are poorly understood, these responses are highly variable between individuals. Using a mouse model, we report that antibiotic-driven intestinal dysbiosis, specifically in early life, leads to significantly impaired antibody responses to five different adjuvanted and live vaccines. Restoration of the commensal microbiota following antibiotic exposure rescues these impaired responses. In contrast, antibiotic-treated adult mice do not exhibit impaired antibody responses to vaccination. Interestingly, in contrast to impaired antibody responses, immunized mice exposed to early-life antibiotics display significantly enhanced T cell cytokine recall responses upon ex vivo restimulation with the vaccine antigen. Our results demonstrate that, in mice, antibiotic-driven dysregulation of the gut microbiota in early life can modulate immune responses to vaccines that are routinely administered to infants worldwide.

Venezuelan equine encephalitis (VEE) virus causes an acute central nervous system infection in human and animals. Melatonin (MLT), minocycline (MIN) and ascorbic acid (AA) have been shown to have antiviral activities in experimental infections; however, the mechanisms involved are poorly studied. Therefore, the aim of this study was to determine the effects of those compounds on the viral titers, NO production and lipid peroxidation in the brain of mice and neuroblastoma cultures infected by VEE virus. Infected mouse (10 LD50) were treated with MLT (500μg /kg bw), MIN (50mg /kg bw) or AA (50mg /kg bwl). Infected neuroblastoma cultures (MOI: 1); MLT: 0.5, 1, 5mM, MIN: 0.1, 0.2, 2μM or AA: 25, 50, 75μM. Brains were obtained at days 1, 3 and 5. In addition, survival rate of infected treated mice was also analyzed. Viral replication was determinedby the plaque formation technique. NO and lipid peroxidation were measured by Griess' reaction and thiobarbituric acid assay respectively. Increased viral replication, NO production and lipid peroxidation were observed in both, infected brain and neuroblastoma cell cultures compared with uninfectedcontrols. Those effects were diminished by the studied treatments. In addition, increased survival rate (50%) in treated infected animals compared with untreated infected mice (0%) was found. MLT, MIN and AA have an antiviral effect involving their anti-oxidant properties, and suggesting a potentialuse of these compounds for human VEE virus infection.