Seasonal influenza split vaccines confer partial cross-protection against heterologous influenza virus in ferrets when combined with the CAF01 adjuvant

Influenza epidemics occur annually, and estimated 5–10% of the adult population and 20–30% of children will become ill from influenza infection. Seasonal vaccines primarily work through the induction of neutralizing antibodies against the principal surface antigen hemagglutinin (HA). This important role of HA-specific antibodies explains why previous pandemics have emerged when new HAs have appeared in circulating human viruses. It has long been recognized that influenza virus-specific CD4(+) T cells are important in protection from infection through direct effector mechanisms or by providing help to B cells and CD8(+) T cells. However, the seasonal influenza vaccine is poor at inducing CD4(+) T-cell responses and needs to be combined with an adjuvant facilitating this response. In this study, we applied the ferret model to investigate the cross-protective efficacy of a heterologous trivalent influenza split-virion (TIV) vaccine adjuvanted with the CAF01 adjuvant, with proven ability to induce CD4(+) T-cell and antibody responses in mice, ferrets, pigs, primates, and humans. Our results indicate that CAF01-adjuvanted vaccine induces HA inhibition (HAI)-independent protection after heterologous challenge, manifested as reduced viral load and fever. On the other hand, we observe increased inflammation in the airways and more neutrophil and mononuclear cell infiltration in these ferrets when compared with optimally protected animals, i.e., ferrets receiving the same vaccine but a homologous challenge. This suggest that HAI-independent immunity induced by TIV + CAF01 can reduce viral shedding and systemic disease symptoms, but does not reduce local inflammation in the nasal cavity

PB1 as a potential target for increasing the breadth of T-cell mediated immunity to Influenza A

Recently, we showed that combined intranasal and subcutaneous immunization with a non-replicating adenoviral vector expressing NP of influenza A, strain PR8, induced long-standing protection against a range of influenza A viruses. However, H-2(b) mice challenged with an influenza A strain mutated in the dominant NP(366) epitope were not efficiently protected. To address this problem, we envision the use of a cocktail of adenovectors targeting different internal proteins of influenza A virus. Consequently, we investigated the possibility of using PB1 as a target for an adenovector-based vaccine against influenza A. Our results showed that PB1 is not as immunogenic as the NP protein. However, by tethering PB1 to the murine invariant chain we were able to circumvent this problem and raise quite high numbers of PB1-specific CD8(+) T cells in the circulation. Nevertheless, mice immunized against PB1 were not as efficiently protected against influenza A challenge as similarly NP-vaccinated animals. The reason for this is not a difference in the quality of the primed cells, nor in functional avidity. However, under similar conditions of immunization fewer PB1-specific cells were recruited to the airways, and surface expression of the dominant PB1 peptide, PB1(703), was less stable than in the case of NP(366)

Risk and Subtypes of Stroke Following New-Onset Postoperative Atrial Fibrillation in Coronary Bypass Surgery:A Population-Based Cohort Study

BACKGROUND: New‐onset postoperative atrial fibrillation (POAF) develops in approximately one‐third of patients undergoing cardiac surgery and is associated with a higher incidence of ischemic stroke and increased mortality. However, it remains unknown to what extent ischemic stroke events in patients with POAF are cardioembolic and whether anticoagulant therapy is indicated. We investigated the long‐term risk and pathogenesis of postoperative stroke in patients undergoing coronary artery bypass grafting experiencing POAF. METHODS AND RESULTS: This was a register‐based cohort study. Data from the WDHR (Western Denmark Heart Registry) were linked with the DNPR (Danish National Patient Register), the Danish National Prescription Register, and the Cause of Death Register. All stroke diagnoses were verified, and ischemic stroke cases were subclassified according to pathogenesis. Furthermore, investigations of all‐cause mortality and the use of anticoagulation medicine for the individual patient were performed. A total of 7813 patients without a preoperative history of atrial fibrillation underwent isolated coronary artery bypass grafting between January 1, 2010, and December 31, 2018, in Western Denmark. POAF was registered in 2049 (26.2%) patients, and a postoperative ischemic stroke was registered in 195 (2.5%) of the patients. After adjustment, there was no difference in the risk of ischemic stroke (hazard ratio [HR], 1.08 [95% CI, 0.74–1.56]) or all‐cause mortality (HR, 1.09 [95% CI, 0.98–1.23]) between patients who developed POAF and non‐POAF patients. Although not statistically significant, patients with POAF had a higher incidence rate (IR; per 1000 patient‐years) of cardioembolic stroke (IR, 1 [95% CI, 0.6–1.6] versus IR, 0.5 [95% CI, 0.3–0.8]), whereas non‐POAF patients had a higher incidence rate of large‐artery occlusion stroke (IR, 1.1 [95% CI, 0.8–1.5] versus IR, 0.7 [95% CI, 0.4–1.4]). Early initiation of anticoagulation medicine was not associated with a lower risk of ischemic stroke. However, patients with POAF were more likely to die of cardiovascular causes than non‐POAF patients (P<0.001). CONCLUSIONS: We found no difference in the adjusted risk of postoperative stroke or all‐cause mortality in POAF versus non‐POAF patients. Patients with POAF after coronary artery bypass grafting presented with a higher, although not significant, proportion of ischemic strokes of the cardioembolic type

Threshold detachment of negative ions by electron impact

The description of threshold fragmentation under long range repulsive forces is presented. The dominant energy dependence near threshold is isolated by decomposing the cross section into a product of a back ground part and a barrier penetration probability resulting from the repulsive Coulomb interaction. This tunneling probability contains the dominant energy variation and it can be calculated analytically based on the same principles as Wannier's description for threshold ionization under attractive forces. Good agreement is found with the available experimental cross sections on detachment by electron impact from $D^{-}$, $O^{-}$ and $B^{-}$.Comment: 4 pages, 4 figures (EPS), to appear in Phys.Rev.Lett, Feb. 22nd, 199

Combined local and systemic immunization is essential for durable T-cell mediated heterosubtypic immunity against influenza A virus

The threat from unpredictable influenza virus pandemics necessitates the development of a new type of influenza vaccine. Since the internal proteins are highly conserved, induction of T cells targeting these antigens may provide the solution. Indeed, adenoviral (Ad) vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. Local (intranasal (i.n.)) immunization elicited delayed, but more lasting protection despite relatively inefficient immunization. However, by far, the most robust protection was induced by simultaneous, combined (i.n. + s.c.) vaccination, and, notably, in this case clinical protection lasted at least 8 months without showing any evidence of fading. Interestingly, the superior ability of the latter group to resist reinfection correlated with a higher number of antigen-specific CD8 T cells in the spleen. Thus, detailed analysis of the underlying CD8 T cell responses highlights the importance of T cells already positioned in the lungs prior to challenge, but at the same time underscores an important back-up role for circulating antigen-specific cells with the capacity to expand and infiltrate the infected lungs

The eSMA: description and first results

The eSMA ("extended SMA") combines the SMA, JCMT and CSO into a single facility, providing enhanced sensitivity and spatial resolution owing to the increased collecting area at the longest baselines. Until ALMA early science observing (2011), the eSMA will be the facility capable of the highest angular resolution observations at 345 GHz. The gain in sensitivity and resolution will bring new insights in a variety of fields, such as protoplanetary/transition disks, high-mass star formation, solar system bodies, nearby and high-z galaxies. Therefore the eSMA is an important facility to prepare the grounds for ALMA and train scientists in the techniques. Over the last two years, and especially since November 2006, there has been substantial progress toward making the eSMA into a working interferometer. In particular, (i) new 345-GHz receivers, that match the capabilities of the SMA system, were installed at the JCMT and CSO; (ii) numerous tests have been performed for receiver, correlator and baseline calibrations in order to determine and take into account the effects arising from the differences between the three types of antennas; (iii) first fringes at 345 GHz were obtained on August 30 2007, and the array has entered the science-verification stage. We report on the characteristics of the eSMA and its measured performance at 230 GHz and that expected at 345 GHz. We also present the results of the commissioning and some initial science-verification observations, including the first absorption measurement of the C/CO ratio in a galaxy at z=0.89, located along the line of sight to the lensed quasar PKS1830-211, and on the imaging of the vibrationally excited HCN line towards IRC+10216.Comment: 12 pages, 7 figures, paper number 7012-12, to appear in Proceedings of SPIE vol. 7012: "Ground-based and Airborne Telescopes II", SPIE conference on Astronomical Instrumentation, Marseille, 23-28 June 200

Detection of CI in absorption towards PKS 1830-211 with the eSMA

We report the first science observations and results obtained with the "extended" SMA (eSMA), which is composed of the SMA (Submillimeter Array), JCMT (James Clerk Maxwell Telescope) and CSO (Caltech Submillimeter Observatory). Redshifted absorptions at z=0.886 of CI (^3P_1 - ^3P_0) were observed with the eSMA with an angular resolution of 0.55"x0.22" at 1.1 mm toward the southwestern image of the remarkable lensed quasar PKS 1830-211, but not toward the northeastern component at a separation of ~1". Additionally, SMA observations of CO, 13CO and C18O (all J=4-3) were obtained toward this object: CO was also detected toward the SW component, but none of the isotopologues were. This is the first time [CI] is detected in this object, allowing the first direct determination of relative abundances of neutral atomic carbon to CO in the molecular clouds of a spiral galaxy at z>0.1. The [CI] and CO profiles can be decomposed into two and three velocity components respectively. We derive C/CO column density ratios ranging from <0.5 (representative of dense cores) to ~2.5 (close to translucent clouds values). This could indicate that we are seeing environments with different physical conditions or that we are witnessing chemical evolution of regions where C has not completely been converted into CO.Comment: 6 pages using emulateapj, 3 tables, 2 figures ; accepted for publication in ApJ