CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines.

Nanoparticle vaccines based on H. pylori ferritin are increasingly used as a vaccine platform for many pathogens, including RSV, influenza, and SARS-CoV-2. They have been found to elicit enhanced, long-lived B cell responses. The basis for improved efficacy of ferritin nanoparticle vaccines remains unresolved, including whether recruitment of CD4 T cells specific for the ferritin component of these vaccines contributes to cognate help in the B cell response. Using influenza HA-ferritin nanoparticles as a prototype, we have performed an unbiased assessment of the CD4 T cell epitope composition of the ferritin particles relative to that contributed by influenza HA using mouse models that express distinct constellations of MHC class II molecules. The role that these CD4 T cells play in the B cell responses was assessed by quantifying follicular helper cells (TFH), germinal center (GC) B cells, and antibody secreting cells. When mice were immunized with equimolar quantities of soluble HA-trimers and HA-Fe nanoparticles, HA-nanoparticle immunized mice had an increased overall abundance of TFH that were found to be largely ferritin-specific. HA-nanoparticle immunized mice had an increased abundance of HA-specific isotype-switched GC B cells and HA-specific antibody secreting cells (ASCs) relative to mice immunized with soluble HA-trimers. Further, there was a strong, positive correlation between CD4 TFH abundance and GC B cell abundance. Thus, availability of helper CD4 T cell epitopes may be a key additional mechanism that underlies the enhanced immunogenicity of ferritin-based HA-Fe-nanoparticle vaccines.

A Brief Intervention to Support Implementation of Telerehabilitation by Community Rehabilitation Services During COVID-19: A Feasibility Study.

The coronavirus disease 2019 (COVID-19) pandemic has necessitated adoption of telerehabilitation in services where face-to-face consultations were previously standard. We aimed to understand barriers to implementing a telerehabilitation clinical service and design a behavior support strategy for clinicians to implement telerehabilitation. A hybrid implementation study design included pre- and post-intervention questionnaires, identification of key barriers to implementation using the theoretical domains framework, and development of a targeted intervention. Thirty-one clinicians completed baseline questionnaires identifying key barriers to the implementation of telerehabilitation. Barriers were associated with behavior domains of knowledge, environment, social influences, and beliefs. A 6-week brief intervention focused on remote clinician support, and education was well received but achieved little change in perceived barriers to implementation. The brief intervention to support implementation of telerehabilitation during COVID-19 achieved clinical practice change, but barriers remain. Longer follow-up may determine the sustainability of a brief implementation strategy, but needs to consider pandemic-related stressors.