mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.
View Article and Find Full Text PDF: Current literature has demonstrated the benefits of transversus abdominis plane (TAP) blocks for reducing postoperative pain and opioid consumption for an array of surgical procedures. Some randomized controlled trials and retrospective studies have compared ultrasound guidance TAP blocks completed by anesthesiologists (US-TAP) to laparoscopic guidance TAP blocks completed by surgeons (LAP-TAP). However, the findings of these studies have not been consolidated to improve recommendations and patient outcomes.
View Article and Find Full Text PDFSaponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies in nonhuman primates (NHPs) comparing the most common clinical adjuvant aluminum hydroxide (alum) with saponin/monophosphoryl lipid A nanoparticles (SMNP), an immune-stimulating complex-like adjuvant. SMNP elicited substantially stronger humoral immune responses than alum, including 7-fold higher peak antigen-specific germinal center B-cell responses, 18-fold higher autologous neutralizing antibody titers, and higher levels of antigen-specific plasma and memory B cells.
View Article and Find Full Text PDFOriginally reserved for those who are profoundly deaf, cochlear implantation is now common for people with partial hearing loss, particularly when combined with a hearing aid. This combined intervention enhances speech comprehension and sound quality when compared to electrical stimulation alone, particularly in noisy environments, but the physiological basis for the benefits is not well understood. Our long-term aim is to elucidate the underlying physiological mechanisms of this improvement, and as a first step in this process, we have investigated in normal hearing cats, the degree to which the patterns of neural activity evoked in the inferior colliculus (IC) by speech sounds in various levels of noise allows discrimination between those sounds.
View Article and Find Full Text PDFDuring infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure.
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