Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques.

Tuberculosis (TB) remains the deadliest infectious disease1, and the widely used Bacillus Calmette-Guérin (BCG) vaccine fails to curb the epidemic. An improved vaccination strategy could provide a cost-effective intervention to break the transmission cycle and prevent antimicrobial resistance2,3. Limited knowledge of the host responses critically involved in protective immunity hampers the development of improved TB vaccination regimens. Therefore, assessment of new strategies in preclinical models to select the best candidate vaccines before clinical vaccine testing remains indispensable. We have previously established in rhesus macaques (Macaca mulatta) that pulmonary mucosal BCG delivery reduces TB disease where standard intradermal injection fails4,5. Here, we show that pulmonary BCG prevents infection by using a repeated limiting-dose Mycobacterium tuberculosis challenge model and identify polyfunctional T-helper type 17 (TH17) cells, interleukin-10 and immunoglobulin A as correlates of local protective immunity. These findings warrant further research into mucosal immunization strategies and their translation to clinical application to more effectively prevent the spread of TB.

In vivo imaging of brain estrogen receptors in rats: a 16α-18F-fluoro-17ß-estradiol PET study.

UNLABELLED: The steroid hormone estrogen is important for brain functioning and is thought to be involved in brain diseases, such as Alzheimer disease and depression. The action of estrogen is mediated by estrogen receptors (ERs). To understand the role of estrogens in brain functioning, it is important to study ERs in the brain. The aims of the present study were to determine whether ERs could be measured in the rat brain by PET with the ER ligand 16α-(18)F-fluoro-17ß-estradiol ((18)F-FES) and to evaluate whether tracer uptake was affected by endogenous estrogen. METHODS: Small-animal PET was used to determine (18)F-FES uptake in female rats in the diestrous phase of the estrous cycle, the proestrous phase, and after ovariectomy. Coinjection of (18)F-FES with 17ß-estradiol was performed to determine whether tracer binding was specific for ERs. Additionally, (18)F-FES uptake was quantified with kinetic modeling in female rats in the proestrous phase and after ovariectomy and in male rats. RESULTS: The highest levels of uptake of (18)F-FES were found (in descending order) in the pituitary, hypothalamus, bed nucleus of the stria terminalis, and amygdala. Other brain regions showed low levels of brain uptake. The level of (18)F-FES uptake was higher in the pituitary and hypothalamus in rats after ovariectomy than in rats in the proestrous phase. Coinjection with 17ß-estradiol resulted in a decrease in (18)F-FES uptake in the pituitary and hypothalamus. The volume of distribution and binding potential determined with kinetic modeling were higher in the pituitary than in the other brain regions in all 3 groups. No differences were found among the groups. CONCLUSION: (18)F-FES PET imaging of ER availability in the rat brain is feasible for brain regions with high ER densities.