| 1. |
- Bardel, Emilie, et al.
(författare)
-
Intradermal immunisation using the TLR3-ligand Poly (I:C) as adjuvant induces mucosal antibody responses and protects against genital HSV-2 infection
- 2016
-
Ingår i: npj Vaccines. - : Springer Science and Business Media LLC. - 2059-0105. ; 1
-
Tidskriftsartikel (refereegranskat)abstract
- © The Author(s) 2016. Development of vaccines able to induce mucosal immunity in the genital and gastrointestinal tracts is a major challenge to counter sexually transmitted pathogens such as HIV-1 and HSV-2. Herein, we showed that intradermal (ID) immunisation with sub-unit vaccine antigens (i.e., HIV-1 gp140 and HSV-2 gD) delivered with Poly(I:C) or CpG1668 as adjuvant induces long-lasting virus-specific immunoglobulin (Ig)-G and IgA antibodies in the vagina and feces. Poly(I:C)-supplemented sub-unit viral vaccines caused minimal skin reactogenicity at variance to those containing CpG1668, promoted a delayed-type hypersensitivity (DTH) to the vaccine and protected mice from genital and neurological symptoms after a lethal vaginal HSV-2 challenge. Interestingly, Poly(I:C 12U) (Ampligen), a Poly(I:C) structural analogue that binds to TLR3 but not MDA-5, promoted robust mucosal and systemic IgG antibodies, a weak skin DTH to the vaccine but not IgA responses and failed to confer protection against HSV-2 infection. Moreover, Poly(I:C) was far superior to Poly(I:C 12U) at inducing prompt and robust upregulation of IFNß transcripts in lymph nodes draining the injection site. These data illustrate that ID vaccination with glycoproteins and Poly(I:C) as adjuvant promotes long-lasting mucosal immunity and protection from genital HSV-2 infection, with an acceptable skin reactogenicity profile. The ID route thus appears to be an unexpected inductive site for mucosal immunity and anti-viral protection suitable for sub-unit vaccines. This works further highlights that TLR3/MDA5 agonists such as Poly(I:C) may be valuable adjuvants for ID vaccination against sexually transmitted diseases.
|
|
| 2. |
- Sanders, Prashanthan, et al.
(författare)
-
Frequency mapping of the pulmonary veins in paroxysmal versus permanent atrial fibrillation
- 2006
-
Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 17, s. 965-972
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The pulmonary veins (PVs) are a dominant source of triggers initiating atrial fibrillation (AF). While recent evidence implicates these structures in the maintenance of paroxysmal AF, their role in permanent AF is not known. The current study aims to compare the contribution of PV activity to the maintenance of paroxysmal and permanent AF. METHODS AND RESULTS: Thirty-four patients with paroxysmal AF (n = 20) or permanent AF (n = 14) undergoing ablation were studied. Prior to ablation, 32 seconds of electrograms were acquired from each PV and the coronary sinus (CS). The frequency of activity of each PV and CS was defined as the highest amplitude frequency on spectral analysis. The effects of ablation on the AF cycle length (AFCL) and frequency and on AF termination were determined. Significant differences were observed between paroxysmal and permanent AF. Paroxysmal AF demonstrates higher frequency PV activity (11.0 +/- 3.1 vs 8.8 +/- 3.0 Hz; P = 0.0003) but lower CS frequency (5.8 +/- 1.2 vs 6.9 +/- 1.4 Hz; P = 0.01) and longer AFCL (182 +/- 17 vs 158 +/- 21 msec; P = 0.002), resulting in greater PV to atrial frequency gradient (7.2 +/- 2.2 vs 4.2 +/- 2.9 Hz; P = 0.006). PV isolation in paroxysmal AF resulted in a greater decrease in atrial frequency (1.0 +/- 0.7 vs -0.05 +/- 0.4 Hz; P < 0.0001), greater prolongation of the AFCL (49 +/- 35 vs 5 +/- 6 msec; P < 0.0001), and more frequent AF termination (11/20 vs 0/14; P = 0.0007) compared to permanent AF. CONCLUSION: Paroxysmal AF is associated with higher frequency PV activity and lesser CS frequency compared to permanent AF. Isolation of the PVs had a greater impact on the fibrillatory process in paroxysmal AF compared to permanent AF, suggesting that while the PVs have a role in maintaining paroxysmal AF, these structures independently contribute less to the maintenance of permanent AF
|
|
| 3. |
|
|
