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Recent emergence of a causal like between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a novel vaccine formulation based on a lymph node targeting Amphiphile (AMP) vaccine adjuvant, AMP-CpG, admixed with EBV gp350 glycoprotein and a novel EBV-polyepitope protein (EBVpoly) that includes 20 CD8+ T-cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses were induced in mice with titers > 100,000 in AMP-CpG vaccinated mice. Immunization including AMP-CpG also induced high frequencies of polyfunctional gp350-specific CD4+ T-cells and EBVpoly-specific CD8+ T-cells that were 2-fold greater than soluble CpG and were maintained for > 7 months post immunization. This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases. Teaser: A lymph node targeted AMP-CpG subunit EBV vaccine induces potent and durable immunity in HLA expressing mice.

Background Individuals with inflammatory bowel disease (IBD) are at increased risk of developing anxiety or depression (A&D). Crohn's disease (CD) and ulcerative colitis (UC) with comorbid A&D are both more challenging to manage. IBD providers need to better understand the causes and impact of A&D in order to improve care for IBD patients. We sought to identify clinical factors that influence development of A&D and healthcare utilization in IBD. Methods This is a retrospective analysis using an IBD natural history registry from a single tertiary care referral center. Presence of A&D was determined based upon responses to the Hospital Anxiety and Depression Scale. Demographic and clinical factors were abstracted to evaluate for significant associations. Results Four hundred thirty-two IBD patients (132 UC, 256 CD, and 44 indeterminate colitis) were included in this study. One hundred ninety-two (44.4%) had anxiety or depression or both, and most were female (59.4%, P < 0.05). History of surgery (P < 0.05), female gender (P < 0.05), smoking (P < 0.05), and extra-intestinal manifestations (P < 0.01) were each independently predictive of A&D. Inflammatory bowel disease patients with A&D more often underwent imaging studies (53.6% vs 36.7%, P < 0.05), visited the ED (30.7% vs 20.8%, P < 0.05), or were hospitalized (31.7% vs 21.7%, P < 0.05). They were also more frequently prescribed corticosteroids (50.5% vs 36.7%, P < 0.01) and biologic medications (62.5% vs 51.3%, P < 0.05). Finally, they were more likely to have had at least 1 "no-show" (29.2% vs 16.7%, P < 0.01) and had a higher mean number of "no-shows" (0.69 +/- 0.1 vs 0.30 +/- 0.1, P < 0.01) over the study period. Discussion Anxiety and depression are common in the setting of IBD and are strongly associated with surgical history, disease complications (including extra-intestinal manifestations), smoking, and female gender. Inflammatory bowel disease patients with A&D are also more likely to require therapy and to utilize healthcare resources. This study refines our understanding of A&D development and its impact in IBD and provides additional considerations for management in this setting.

Mesoporous silica nanoparticles (MSN) have potential as drug delivery and controlled release devices due to their high surface area and absorption capabilities. The effect of surface charge and pH on the release of the fluorescent dye, rhodamine 6G, from MSN has been studied. Release profiles of rhodamine 6G from bare and amine-coated MSN at pH 5.0 and 7.4 are very different and demonstrate that electrostatic interactions between entrapped rhodamine 6G molecules and the charged surface of the MSN have a significant effect on release kinetics. Release of rhodamine 6G from amine-coated MSN can be fit to a single exponential function, while release from bare MSN can be fit to a double exponential function—indicating that the release of rhodamine 6G from bare MSN is a two-phase process. In addition, it was determined that MSN need to be sonicated in dye solution to maximize their loading capacity.

Microneedle skin patches represent a promising approach for safe, convenient, and rapid delivery of vaccines and therapeutics to the skin through pain-free disruption of the stratum corneum to access epidermal and dermal immune-competent cell populations. We have developed a ‘nano-layer’-coated microneedle (MN) delivery platform in which vaccines/therapeutics encapsulated in surface coatings on biodegradable polymer MNs are rapidly delivered upon application to the skin of mice. Layer-by-layer deposition of plasmid DNA (pDNA) and nucleic acid TLR agonists together with biodegradable polymers on the surface of microneedle arrays gave thin coatings with tunable dosages of vaccine cargo and vaccine release rates. Following application of coated MN arrays to the skin of mice for ~5 min, intact film coatings were rapidly implanted in the skin for sustained release of vaccine components over time. Microneedle delivery of DNA vaccines encoding SIV-gag proteins induced 5-fold increased antigen-specific T-cell expansion and generation of serum IgG titers 5-fold in excess of that observed for traditional i.m. or i.d. immunizations; further, responses obtained with MN delivery were quantitatively similar to those observed for i.m. delivery with in vivo electroporation. MN delivery also induced enhanced generation of long-lived memory T-cells. Together these results demonstrate the potential for MN delivery to improve vaccine performance in the context of HIV immunization.

Seitdem sich C. G. Jacobi in seiner Abhandlung „De compositione numerorum e quatuor quadratis“ mit der elementaren Form x 2 + y 2 + z 2 + t 2 auseinandersetzte, sind hinsichtlich des Problems der Anzahl der Darstellungen naturlicher Zahlen durch ganz rationale quaternare quadratische Formen wesentliche Fortschritte erzielt worden. Vor allem im vergangenen Jahrzehnt konnten durch G. Aeberli, H. Gross, O. Weber, K. Germann und E. Benz wertvolle Resultate gewonnen werden mittels der Theorie der Theta-Funktionen und der Theorie der Quaternionen-Algebren.