Assessment of In Vitro Immunostimulatory Activity of an Adjuvanted Whole-Cell Inactivated Neisseria gonorrhoeae Microparticle Vaccine Formulation.

The emergence of drug-resistant gonorrhea infections worldwide combined with the lack of a vaccine is alarming. We prepared a novel microparticulate (MP) vaccine formulation using whole-cell inactivated Neisseria gonorrhoeae as the vaccine antigen, with Alum and AddaVax™ as vaccine adjuvants. The adjuvanted vaccine MP formulation was assessed for in vitro immunostimulatory activity, autophagy, and antigen presentation ability. The data shows that the adjuvanted gonococci vaccine MP enhanced autophagy induction in antigen presenting cells (APCs) compared to gonococci vaccine MP without adjuvants, which is important for enhancing antigen presentation. In addition, the adjuvanted vaccine formulation increased the surface expression of antigen presenting molecules MHCI and MHCII as well as co-stimulatory molecules CD40 and CD86 on the surface of dendritic cells. In addition, the gonococci vaccine microparticles at lower doses did not significantly increase the expression of the death receptor CD95 in APCs, which when elevated leads to suboptimal antigen presentation and reduced immune responses. The adjuvanted whole-cell inactivated gonococci microparticle vaccine formulation enhanced antigen uptake, processing, and antigen presentation.

Assessment of the Role of Serum 25-Hydroxy Vitamin D Level on Coronary Heart Disease Risk With Stratification Among Patients With Type 2 Diabetes Mellitus.

We investigated the role of vitamin D on glycemic regulation and cardiac complications in patients with type 2 diabetes mellitus (T2DM). A total of 1139 patients (49.3% males vs 50.7% females) were included. Information on sociodemographic lifestyle, family history, blood pressure (BP), and coronary heart disease (CHD) complications was collected. Significant differences were found between males and females regarding age-groups (P = .002), body mass index (BMI; P = .008), physical activity (P = .010), sheesha smoking (P = .016), cigarette smoking (P = .002), hypertension (P = .050), metabolic syndrome (P = .026), and CHD (P = .020). There were significant differences between vitamin D deficiency, insufficiency, and sufficiency in relation to age-group (P = .002), income (P = .002), waist circumference (P = .002), hip circumference (P = .028), waist-hip ratio (P = .002), and BMI (P = .002). Further, mean values of hemoglobin, magnesium, creatinine, hemoglobin A1c (HbA1c), total cholesterol, uric acid, and diastolic BP were significantly higher among patients with vitamin D deficiency compared with those with insufficiency and sufficiency. Multiple logistic regression analysis revealed that 25-hydroxy vitamin D, 25(OH)D, HbA1c, waist circumference, uric acid, duration of T2DM, total cholesterol, systolic and diastolic BP, and BMI were strong predictor risk factors for CHD among patients with T2DM. The present study supports that 25(OH)D may have a direct effect on CHD and on its risk factors.

Incidence of macrolide resistance in Streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine: population-based assessment.

BACKGROUND: The prevalence of macrolide resistance in Streptococcus pneumoniae has risen in recent years after the introduction of new macrolides and their increased use. We assessed emergence of macrolide-resistant invasive S pneumoniae disease in Atlanta, GA, USA, before and after the licensing, in February 2000, of the heptavalent pneumococcal conjugate vaccine for young children. METHODS: Prospective population-based surveillance was used to obtain pneumococcal isolates and demographic data from patients with invasive pneumococcal disease. We calculated cumulative incidence rates for invasive pneumococcal disease for 1994-2002 using population estimates and census data from the US Census Bureau. FINDINGS: The incidence of invasive pneumococcal disease in Atlanta fell from 30.2 per 100,000 population (mean annual incidence 1994-99) to 13.1 per 100,000 in 2002 (p<0.0001). Striking reductions were seen in children younger than 2 years (82% decrease) and in those 2-4 years (71% decrease), age-groups targeted to receive pneumococcal conjugate vaccine. Significant declines were also noted in adults aged 20-39 (54%), 40-64 (25%), and 65 years and older (39%). Macrolide resistance in invasive S pneumoniae disease in Atlanta, after increasing steadily from 4.5 per 100,000 in 1994 to 9.3 per 100,000 in 1999, fell to 2.9 per 100,000 by 2002. Reductions in disease caused by mefE-mediated and erm-mediated macrolide-resistant isolates of conjugate-vaccine serotypes 6B, 9V, 19F, and 23F, and the vaccine-associated serotype 6A were also recorded. INTERPRETATION: Vaccines can be a powerful strategy for reducing antibiotic resistance in a community.