Formulation of aluminum hydroxide adjuvant with TLR agonists poly(I:C) and CpG enhances the magnitude and avidity of the humoral immune response.

Subunit vaccines generally require adjuvants to achieve optimal immune responses. Toll-like receptor (TLR) agonists are promising immune potentiators, but rapid diffusion from the injection site reduces their local effective concentration and may cause systemic reactions. In this study, we investigated the potential of aluminum hydroxide adjuvant (AH) to adsorb the TLR3 agonist poly(I:C) and TLR9 agonist CpG and compared the effect of the combination adjuvant on the immune response with either the TLR agonists or AH alone in mice. Poly(I:C) and CpG readily adsorbed onto AH and this combination adjuvant induced a stronger IgG1 and IgG2a immune response with a significant increase of antibody avidity. The combination adjuvant enhanced antigen uptake and activation of dendritic cells in vitro. It induced an inflammatory response at the injection site similar to AH but without eosinophils which are typically observed with AH. A distinctive antigen-containing monocyte/macrophage population with an intermediate level of CD11c expression was identified in the draining lymph nodes after immunization with TLR agonists and the combination adjuvant. Injection of the combination adjuvant did not induce an increase of TNFα and CXCL10 in serum in contrast to the injection of soluble TLR agonists. These results indicate that this combination adjuvant is a promising formulation to solve some of the unmet needs of current vaccines.

Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells.

Biodegradable nanoparticles with functionalized surfaces are attractive candidates as vaccine adjuvants. Nano-11 are cationic dendrimer-like α-D-glucan nanoparticles with a diameter of 70-80 nm. Mice injected with antigen formulated with Nano-11 developed antibody titers that were similar or greater than antigen with aluminum adjuvant. Utilizing an in vivo imaging system, Nano-11 was shown to remain at the injection site after administration and cleared gradually over the course of 3 weeks. Injection of Nano-11 induced a transient inflammatory response characterized by recruitment of a mixed population of inflammatory cells, predominantly monocytes and macrophages with relatively few neutrophils. Recruited Mac-2+macrophages efficiently phagocytized the majority of Nano-11 at the injection site. Fluorescently labeled Nano-11 was present in cells in the draining lymph nodes 1 day after injection, with the majority contained in migratory dendritic cells. Injection of ovalbumin adsorbed to Nano-11 resulted in an increase of ovalbumin-containing cells in draining lymph nodes. Nano-11 delivered more antigen to antigen-presenting cells on a per cell basis and demonstrated more specific targeting to highly immunopotentiating migratory dendritic cells compared with soluble or aluminum hydroxide adsorbed ovalbumin. These results support the efficacy of Nano-11 and its potential use as a next generation vaccine adjuvant.

An intensive intervention for improving gait, balance, and mobility in individuals with chronic incomplete spinal cord injury: a pilot study of activity tolerance and benefits.

OBJECTIVE: To determine the tolerance to and benefits of an intensive mobility training (IMT) approach for individuals with incomplete spinal cord injury (ISCI). DESIGN: Prospective pretest-posttest study with 6-month follow-up. SETTING: University research laboratory. PARTICIPANTS: A volunteer sample of individuals with ISCI (N=15; >6 mo postinjury and able to walk at least 3.05 m with or without assistance). Follow-up data were collected for 10 of the participants. INTERVENTIONS: Participants received IMT for 3h/d for 10 weekdays, participating in activities that encouraged repetitive, task-specific training of their lower extremities in a massed practice schedule. MAIN OUTCOME MEASURES: Amount of time spent in therapeutic activities and rest was used to assess participants' tolerance to the intervention. Treatment outcomes were assessed pretest, posttest, and 6 months after the intervention and included the Berg Balance Scale (BBS), Dynamic Gait Index (DGI), 6-minute walk test, gait speed, and Spinal Cord Injury Functional Ambulation Inventory. RESULTS: Individuals in the higher functioning ISCI group (BBS score ≥45 and gait speed ≥0.6 m/s) spent more time in the intensive therapy on average than individuals in the lower functioning ISCI group. Effect sizes were comparable for changes in balance and mobility assessments between the lower and higher functioning groups, with the largest effect sizes observed for the DGI. CONCLUSIONS: This dosage of IMT may be a more appropriate treatment approach for higher functioning ISCI individuals, as they were better able to tolerate the length of the session and demonstrated higher effect sizes postintervention.