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Measles remains an important cause of childhood mortality worldwide. Sustained high vaccination coverage is the key to preventing measles deaths. Because measles vaccine is delivered by injection, hurdles to high coverage include the need for trained medical personnel and a cold chain, waste of vaccine in multidose vials and risks associated with needle use and disposal. Respiratory vaccine delivery could lower these barriers and facilitate sustained high coverage. We developed a novel single unit dose, dry powder live-attenuated measles vaccine (MVDP) for respiratory delivery without reconstitution. We tested the immunogenicity and protective efficacy in rhesus macaques of one dose of MVDP delivered either with a mask or directly intranasal with two dry powder inhalers, PuffHaler and BD Solovent. MVDP induced robust measles virus (MeV)-specific humoral and T-cell responses, without adverse effects, which completely protected the macaques from infection with wild-type MeV more than one year later. Respiratory delivery of MVDP was safe and effective and could aid in measles control.

The ventromedial prefrontal cortex (vmPFC) has been implicated in fear extinction [Phelps, E. A., Delgado, M. R., Nearing, K. I. & Ledoux, J. E. (2004) Neuron 43, 897-905; Herry, C. & Garcia, R. (2003) Behav. Brain Res . 146, 89-96]. Here, we test the hypothesis that the cortical thickness of vmPFC regions is associated with how well healthy humans retain their extinction memory a day after having been conditioned and then extinguished. Fourteen participants underwent a 2-day fear conditioning and extinction protocol. The conditioned stimuli (CSs) were pictures of virtual lights, and the unconditioned stimulus (US) was an electric shock. On day 1, participants received 5 CS+US pairings (conditioning), followed by 10 CS trials with no US (extinction). On day 2, the CS was presented alone to test for extinction memory. Skin conductance response (SCR) was the behavioral index of conditioning and extinction. Participants underwent MRI scans to obtain structural images, from which cortical thickness was measured. We performed a vertex-based analysis across the entire cortical surface and a region-of-interest analysis of a priori hypothesized territories to measure cortical thickness and map correlations between this measure and SCR. We found significant, direct correlation between thickness of the vmPFC, specifically medial orbitofrontal cortex, and extinction retention. That is, thicker medial orbitofrontal cortex was associated with lower SCR to the conditioned stimulus during extinction recall (i.e., greater extinction memory). These results suggest that the size of the vmPFC might explain individual differences in the ability to modulate fear among humans.