Adjuvant effect of TLR7 agonist adsorbed on aluminum hydroxide (AS37): A phase I randomized, dose escalation study of an AS37-adjuvanted meningococcal C conjugated vaccine.

An adjuvant system (AS37) has been developed containing a synthetic toll-like receptor agonist (TLR7a). We conducted a phase I randomized, observer-blind, dose-escalation study to assess the safety and immunogenicity of an investigational AS37-adjuvanted meningococcus C (MenC) conjugate vaccine in healthy adults (NCT02639351). A control group received a licensed MenC conjugate alum-adjuvanted vaccine. Eighty participants were randomized to receive one dose of control or investigational vaccine containing AS37 (TLR7a dose 12.5, 25, 50, 100 µg). All vaccines were well tolerated, apart from in the TLR7a 100 µg dose group, which had three reports (18.8%) of severe systemic adverse events. Four weeks after vaccination, human complement serum bactericidal assay seroresponse rates against MenC were 56-81% in all groups, and ELISA seroresponses were ≥81% for all AS37-adjuvanted vaccine groups (100% in 50 and 100 µg dose groups) and 88% in the control group. Antibody responses were maintained at six months after vaccination.

Robot-assisted image-guided transcranial magnetic stimulation for somatotopic mapping of the motor cortex: a clinical pilot study.

PURPOSE: Shape and exact location of motor cortical areas varies among individuals. The exact knowledge of these locations is crucial for planning of neurosurgical procedures. In this study, we have used robot-assisted image-guided transcranial magnetic stimulation (Ri-TMS) to elicit MEP response recorded for individual muscles and reconstruct functional motor maps of the primary motor cortex. METHODS: One healthy volunteer and five patients with intracranial tumors neighboring the precentral gyrus were selected for this pilot study. Conventional MRI and fMRI were obtained. Transcranial magnetic stimulation was performed using a MagPro X100 stimulator and a standard figure-of-eight coil positioned by an Adept Viper s850 robot. The fMRI activation/Ri-TMS response pattern were compared. In two cases, Ri-TMS was additionally compared to intraoperative direct electrical cortical stimulation. RESULTS: Maximal MEP response of the m. abductor digiti minimi was located in an area corresponding to the "hand knob" of the precentral gyrus for both hemispheres. Repeated Ri-TMS measurements showed a high reproducibility. Simultaneous registration of the MEP response for m. brachioradialis, m. abductor pollicis brevis, and m. abductor digiti minimi demonstrated individual peak areas of maximal MEP response for the individual muscle groups. Ri-TMS mapping was compared to the corresponding fMRI studies. The areas of maximal MEP response localized within the "finger tapping" activated areas by fMRI in all six individuals. CONCLUSIONS: Ri-TMS is suitable for high resolution non-invasive preoperative somatotopic mapping of the motor cortex. Ri-TMS may help in the planning of neurosurgical procedures and may be directly used in navigation systems.

H-coil: Induced electric field properties and input/output curves on healthy volunteers, comparison with a standard figure-of-eight coil.

OBJECTIVE: To acquire information about the physical properties and physiological effects of the H-coil. METHODS: We used a robotized system to measure the electric field (E-field) generated by a H-coil prototype and compared it with a standard figure-of-eight coil. To explore the physiological properties of the coils, input/output curves were recorded for the right abductor digiti minimi muscle (ADM) as target muscle. To explore focality of stimulation, simultaneous recordings were performed for the left ADM, right abductor pollicis brevis (APB), extensor digitorum communis (EDC) and biceps brachii (BB) muscles. RESULTS: Physical measurements of the H-coil showed four potentially stimulating foci, generating different electric field intensities along two different spatial orientations. RMT was significantly lower for H-coil- as compared to figure-of-eight coil stimulation. When stimulation intensity for the input-output curve was determined by percent of maximum stimulator output, the H-coil produced larger MEPs in the right ADM, as compared to the figure-of-eight coil, due to the larger relative enhancement of stimulation intensity of the H-coil. When stimulation intensity was adjusted to RMT, MEPs elicited at the right ADM were larger for figure-of-eight coil than for H-coil stimulation, while this relation was reversed for distant non-target muscles, with low stimulation intensities. With high stimulation intensities, the H-coil elicited larger MEPs for all tested muscles. Onset latency of the MEPs was never shorter for H-coil than for figure-of-eight coil stimulation of the target muscles. CONCLUSIONS: These results are in favor for a non-focal, but not deeper effect of the H-coil, as compared to a figure-of-eight coil. SIGNIFICANCE: This is the first neurophysiological study exploring the focality and depth of stimulation delivered by the H-coil systematically in humans. We found no advantage of this coil with regard to depth of stimulation in comparison to the figure-of-eight coil. Future studies have to show if the non-focality of this coil differs relevantly from that of other non-focal coils, e.g. the round coil.