Improvement of Islet Engrafts via Treg Induction Using Immunomodulating Polymeric Tolerogenic Microparticles.

Type 1 diabetes (T1D) is a life-threatening condition for which islet transplantation offers a way to extend longevity and vastly improve quality of life, but the degree and duration of success can vary greatly due to the patient's protective immunity against foreign material. The field is in need of cellular engineering modalities to promote a localized, tolerogenic environment to protect transplanted islet tissue. Artificial antigen-presenting cells (aAPCs) can be designed exogenously to mimic immune cells, such as dendritic cells, and administered to patients, allowing greater control over T cell differentiation. As regulatory T cell (Treg) modulation can reduce the activity of cytotoxic T-effector populations, this strategy can be used to promote immune acceptance of both biomaterials and cellular transplants, such as islets. A new class of poly(lactic-co-glycolic acid) (PLGA) and PLGA/PBAE-blend aAPCs containing transforming growth factor beta and conjugated with anti-CD3 and anti-CD28 antibodies, called tolerogenic aAPCs (TolAPCs), are specifically designed to generate a tolerogenic response by inducing Tregs. We characterized TolAPCs' physical and chemical properties via advanced particle imaging and sizing modalities and investigated their impact on the local and systemic immune system across BALB/c and C57BL/6 mouse strains as well as healthy male and female mice via histologic, gene expression, and immunofluorescence staining methods. Strain-specific differences were observed, whereas sex made no difference in the TolAPC response. TolAPCs stimulated the expansion of FOXP3+ Tregs and provided islet cell protection, maintaining improved glucose-stimulated insulin secretion in vitro when co-cultured with cytotoxic CD8+ T cells. We also explored the ability of this TolAPC platform to promote tolerance in a streptozotocin-induced murine T1D C57BL/6 mouse model. We achieved partial islet protection over the first few days following co-injection with PLGA/PBAE TolAPCs; however, grafts failed soon thereafter. Analysis of the local injection site demonstrated that other immune cell types, including APCs and cytotoxic natural killer cells, increased in the islet injection site. While we aimed to promote a localized tolerogenic microenvironment in vivo using biodegradable TolAPCs to induce Tregs and extend islet transplant durability, further TolAPC improvements will be required to both elongate efficacy and control additional immune cell responders.

Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: A systematic review.

BACKGROUND: Pregnant women and their infants under 6 months of age infected with influenza have a high risk of serious morbidity and mortality. Influenza vaccine during pregnancy offers 3-for-1 benefits to pregnant women, fetuses and newborn infants. Current vaccination uptake rates during pregnancy, however, are often lower than other high-risk groups and the general population. METHODS: We systematically reviewed evidence on the effectiveness of interventions to improve influenza vaccination coverage in pregnant women. Risk differences (RDs) were calculated from the included studies. RESULTS: Eleven studies were included in the review, of which four were randomized controlled trials (RCTs). Three cohort studies assessed provider-focused interventions while four RCTs and one cohort study evaluated pregnant women-focused interventions. Two cohort studies and a prospective intervention study assessed the effectiveness of bundled interventions. No study solely assessed the effectiveness of interventions to enhance access to influenza vaccination. One moderate quality RCT showed that an influenza pamphlet, with or without a verbalized benefit statement, improved the vaccination rate (RD=0.26; RD=0.39). The other reviewed RCTs showed discordant results, with RDs ranging from -0.15 to 0.03. Although all observational studies significantly improved vaccination rates (RDs ranged from 0.03 to 0.44), the quality of the evidence varied. CONCLUSIONS: There is a lack of effective interventions to increase the influenza vaccination rate in pregnant women. Based on the existing research, we recommend that clinicians provide influenza pamphlets to pregnant women with a verbalized statement about the benefits of influenza vaccine to newborns. Further high-quality RCTs are needed to develop successful maternal influenza vaccination programs. Increased clarity in reporting the content of interventions would help to improve the comparability and generalizability of the published studies.

Influenza-like illness among Hong Kong Chinese pregnant women.

We assessed the self-reported prevalence of influenza-like illness (ILI) during pregnancy in two samples of 546 and 2764 new mothers who were pregnant during the 2009-10 and 2010-11 peak influenza seasons. During pregnancy, 11% of participants experienced an ILI. Cough, sore throat and nasal congestion were the most common reported symptoms. Only 4.6% and 9% of the participants in sample 1 and 2 had an underlying chronic illness, respectively, and 3.3% of mothers in both groups were smokers. Conducting regular surveillance on influenza prevalence during pregnancy is essential to evaluate the costs and benefits of influenza vaccination programmes.

Brief education to increase uptake of influenza vaccine among pregnant women: a study protocol for a randomized controlled trial.

BACKGROUND: Pregnant women are the highest priority group for annual influenza vaccination. Studies have shown unacceptably low uptake of both seasonal and pandemic A/H1N1 influenza vaccination among pregnant women. This paper will describe the study protocol and methodology of a randomised controlled trial designed to assess the effectiveness of a brief educational intervention in improving the uptake of seasonal influenza vaccine among pregnant women in Hong Kong. METHODS: A randomised controlled trial will be conducted with pregnant women in at least the second trimester of pregnancy from four publicly funded hospital antenatal clinics in Hong Kong. Participants will be randomly assigned to either one of the two treatment groups: standard care (control) or standard care plus brief education (intervention). Pregnant women in the standard care group will receive the usual antenatal care with an educational pamphlet developed by the Hong Kong Centre for Health Protection and those in the intervention group will be provided with usual care plus a brief ten-minute education intervention. Content of the education session will cover four core components recommended in the research literature. The primary study outcome will be the proportion of participants who have received influenza vaccine during their pregnancy. A total of 184 pregnant women (92 per group) will be required to give an 80% power to detect a treatment effect of 15%. DISCUSSION: Most intervention studies aimed at improving influenza vaccination rates in pregnant women have targeted obstetric-care providers and the results of the two patient-oriented RCT interventions are conflicting. The high priority for vaccination given to pregnant women and the low influenza vaccination rate among pregnant women worldwide strongly indicates a need for interventions to improve uptake.