Nanoparticle vaccines were produced using layer-by-layer fabrication and incorporating respiratory syncytial virus (RSV) G protein polypeptides comprising the CX3C chemokine motif. BALB/c mice immunized with G protein nanoparticle vaccines produced a neutralizing antibody response that inhibited RSV replication in the lungs following RSV challenge. ELISPOT analysis showed that G nanoparticle vaccinated mice had increased levels of RSV G protein-specific IL-4 and IFN-γ secreting cells compared to controls following RSV challenge. Remarkably, RSV challenge of G protein nanoparticle vaccinated mice resulted in increased RSV M2-specific IL-4 and IFN-γ secreting T cells, and increased M2-specific H-2Kd-tetramer positive CD8+ T cells in the lungs compared to controls. Cell type analysis showed vaccination was not associated with increased pulmonary eosinophilia following RSV challenge. These results demonstrate that vaccination of mice with the RSV G protein nanoparticle vaccines induces a potent neutralizing antibody response, increased G protein- and M2- specific T cell responses, and a reduction in RSV disease pathogenesis.

Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children; however no effective treatment or vaccine is currently available. Previous studies have shown that therapeutic treatment with a monoclonal antibody (clone 131-2G) specific to the RSV G glycoprotein CX3C motif, mediates virus clearance and decreases leukocyte trafficking to the lungs of RSV-infected mice. In this study, we show that vaccination with layer-by-layer nanoparticles (LbL-NP) carrying the G protein CX3C motif induces blocking antibodies that prevent the interaction of the RSV G protein with the fractalkine receptor (CX3CR1) and protect mice against RSV replication and disease pathogenesis. Peptides with mutations in the CX3C motif induced antibodies with diminished capacity to block G protein-CX3CR1 binding. Passive transfer of these anti-G protein antibodies to mice infected with RSV improved virus clearance and decreased immune cell trafficking to the lungs. These data suggest that vaccination with LbL-NP loaded with the CX3C motif of the RSV G protein can prevent manifestations of RSV disease by preventing the interaction between the G protein and CX3CR1 and recruitment of immune cells to the airways.

A direct consequence of cellular movement and navigation, migration incorporates elements of speed, direction, and persistence of motion. Current techniques to parameterize the trajectory of a chemotaxing cell most commonly pair migration speed with some measure of persistence by calculating MSD, RMS speed, TAD, and/or CI. We address inherent limitations in TAD and CI for comparative analysis by introducing two new analytical tools to quantify persistence: directionality index and directionality time. With the use of these tools, we show that the mechanical properties of the underlying substrate contribute significantly to the regulation of human neutrophil chemotaxis toward fMLP on Fgn-, Col-, and Fn-coated gels of varying elasticity. The β₁-integrin ligand Col demonstrated mechanosensitive speed. In contrast, β₂-integrin ligand Fgn supported mechanosensitive persistence. Fn, recognized by β₁ and β₂ integrins, mechanoregulated speed and persistence. Blocking β₂ integrins of cells migrating on Fn identified an underlying β₂-integrin-directed modulation of persistence. These data demonstrate that individual components of the neutrophil chemotactic response show integrin dependence and are finely tunable with different ligand, mechanotactic, and chemotactic cues, underscoring the need for sensitive analytical methods.

Background: The study objective was to describe the emotional and behavioural responses to Creutzfeldt-Jakob disease (CJD) risk notification. Methods: A qualitative study using 11 participants’ interviews, which were analysed thematically with Framework Analysis. Participants: Six participants purposively selected from people exposed to surgical instruments used previously on patients with or at risk of CJD (any type; n = 60), and 5 participants from a cohort of blood donors to patients who subsequently developed variant CJD (n = 110). Results: Notification was initially a shocking event, but with no lasting emotional impact. Those notified were convinced they were at extremely low risk of CJD and coped by not thinking about the information. Disclosure outside the immediate family was limited by fears of stigma. All expressed concern about the possibility of onward transmission and agreed notification was appropriate. Individual adherence to public health precautions varied from those who did nothing, apart from not donating blood, to those who consistently followed all advice given. This variation was informed by an assumption that information was always shared among health professionals. Conclusions: Factors contributing to minimising emotional distress following notification of CJD risk were evident. We found little evidence of sustained emotional distress. However, implementation of behaviours to minimise onward transmission, particularly in health care settings, was variable – this requires further investigation.

Respiratory syncytial virus (RSV) is the leading cause of serious lower respiratory track illness causing bronchiolitis and some mortality in infants and the elderly. Despite decades of research there is no licensed RSV vaccine. To enable the development of RSV vaccines, several major obstacles must be overcome including immature and waning immunity to RSV infection, the capacity of RSV to evade immunity and the failure of RSV infection to induce robust enduring immunity. Since the failure of the formalin-inactivated RSV vaccine trial, more cautious and deliberate progress has been made toward RSV vaccine development using a variety of experimental approaches. The scientific rational and the state of development of these approaches are reviewed in this article.