Effect of Preexisting Neutralizing Antibodies on the Anti-tumor Immune Response Induced by Chimeric Human Papillomavirus Virus-like Particle Vaccines

AbstractChimeric human papillomavirus virus-like particles (HPV cVLPs) carrying HPV16 E7 protein are potent vaccines for inducing cell-mediated immunity (CMI) against HPV-induced tumors in animal models. We tested the hypothesis that virion-neutralizing antibodies generated during an initial vaccination might prevent effective boosting of CMI to the cVLPs. Mice with circulating HPV16-neutralizing antibodies, generated by direct immunization with wild-type VLPs or by passive transfer of hyperimmune anti-HPV16 VLP mouse sera, were subsequently vaccinated with HPV16 E7-containing cVLPs. Mice with preexisting neutralizing antibodies were not protected from HPV16 E7-positive TC-1 tumor challenge, compared to the protection seen in mice lacking these antibodies. Antibody-coated VLPs bound very inefficiently to receptor-positive cell lines, suggesting that one of the mechanisms of antibody interference is blocking of VLP binding to its receptor and thereby uptake of VLPs by antigen-presenting cells. Our results suggest that repetitive vaccination with a cVLP for induction of cellular immune responses to an incorporated antigen may be of limited effectiveness due to the presence of neutralizing antibodies against the capsid proteins induced after the first application. This limitation could potentially be overcome by boosting with cVLPs containing the same target antigen incorporated into other papillomavirus-type VLPs

Reducing back exertion and improving confidence of individuals with low back pain with a back exosuit: a feasibility study for use in BACPAC

OBJECTIVE: Low back pain (LBP) is hallmarked by activity limitations, especially for tasks involving bending. Back exosuit technology reduces low back discomfort and improves self-efficacy of individuals with LBP during bending and lifting tasks. However, the biomechanical efficacy of these devices in individuals with LBP is unknown. This study sought to determine biomechanical and perceptual effects of a soft active back exosuit designed to assist individuals with LBP sagittal plane bending. To understand patient-reported usability and use cases for this device. METHODS: Fifteen individuals with LBP performed two experimental lifting blocks once with and without an exosuit. Trunk biomechanics were measured by muscle activation amplitudes, and whole-body kinematics and kinetics. To evaluate device perception, participants rated task effort, low back discomfort, and their level of concern completing daily activities. RESULTS: The back exosuit reduced peak back extensor: moments by 9%, and muscle amplitudes by 16% when lifting. There were no changes in abdominal co-activation and small reductions maximum trunk flexion compared to lifting without an exosuit. Participants reported lower task effort, back discomfort, and concern about bending and lifting with an exosuit compared to without. CONCLUSIONS: This study demonstrates a back exosuit not only imparts perceptual benefits of reduced task effort, discomfort, and increased confidence in individuals with LBP but that it achieves these benefits through measurable biomechanical reductions in back extensor effort. The combined effect of these benefits implies back exosuits might be a potential therapeutic aid to augment physical therapy, exercises, or daily activities.UH2 AR076731 - NIAMS NIH HHS; UH3 AR076731 - NIAMS NIH HHSPublished versio

TESTING A MODEL OF EDUCATIONAL PRODUCTIVITY.

TESTING A MODEL OF EDUCATIONAL PRODUCTIVITY