Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy

Fundamental Science Investigations to Develop a 6-MV Laser Triggered Gas Switch for ZR: First Annual Report.

In October 2005, an intensive three-year Laser Triggered Gas Switch (LTGS) development program was initiated to investigate and solve observed performance and reliability issues with the LTGS for ZR. The approach taken has been one of mission-focused research: to revisit and reassess the design, to establish a fundamental understanding of LTGS operation and failure modes, and to test evolving operational hypotheses. This effort is aimed toward deploying an initial switch for ZR in 2007, on supporting rolling upgrades to ZR as the technology can be developed, and to prepare with scientific understanding for the even higher voltage switches anticipated needed for future high-yield accelerators. The ZR LTGS was identified as a potential area of concern quite early, but since initial assessments performed on a simplified Switch Test Bed (STB) at 5 MV showed 300-shot lifetimes on multiple switch builds, this component was judged acceptable. When the Z{sub 20} engineering module was brought online in October 2003 frequent flashovers of the plastic switch envelope were observed at the increased stresses required to compensate for the programmatically increased ZR load inductance. As of October 2006, there have been 1423 Z{sub 20} shots assessing a variety of LTGS designs. Numerous incremental and fundamental switch design modifications have been investigated. As we continue to investigate the LTGS, the basic science of plastic surface tracking, laser triggering, cascade breakdown, and optics degradation remain high-priority mission-focused research topics. Significant progress has been made and, while the switch does not yet achieve design requirements, we are on the path to develop successively better switches for rolling upgrade improvements to ZR. This report summarizes the work performed in FY 2006 by the large team. A high-level summary is followed by detailed individual topical reports

Predictors of survival after vaccination in a pneumonic plague model

Background: The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Methods: Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination. We varied vaccine type, as either a genetic fusion of the F1 and V protein antigens or a mixture of these two recombinant antigens, as well as antigen dose-level and formulation in order to correlate immune response to survival. Results: Whilst there was interaction between each of the variables of vaccine type, dose level and formulation and these all contributed to survival, vaccine formulation in protein-coated microcrystals (PCMCs) was the key contributor in inducing antibody titres. From these data, we propose a cut-off in total serum antibody titre to the F1 and V proteins of 100 µg/mL and 200 µg/mL, respectively. At these thresholds, survival is predicted in this murine pneumonic model to be >90%. Within the total titre of antibody to the V antigen, the neutralising antibody component correlated with dose level and was enhanced when the V antigen in free form was formulated in PCMCs. Antibody titre to F1 was limited by fusion to V, but this was compensated for by PCMC formulation. Conclusions: These data will enable clinical assessment of this and other candidate plague vaccines that utilise the same vaccine antigens by identifying a target antibody titre from murine models, which will guide the evaluation of clinical titres as serological surrogate markers of efficacy

Croatia: Submerged Prehistoric Sites in a Karstic Landscape

Croatia has a long history of underwater archaeological research, especially of shipwrecks and the history of sea travel and trade in Classical Antiquity, but also including intermittent discoveries of submerged prehistoric archaeology. Most of the prehistoric finds have been discovered by chance because of construction work and development at the shore edge or during underwater investigations of shipwrecks. Eustatic sea-level changes would have exposed very extensive areas of now-submerged landscape, especially in the northern Adriatic, of great importance in the Palaeolithic and early Mesolithic periods. Because of sinking coastlines in more recent millennia, submerged palaeoshorelines and archaeological remains of settlement activity extend as late as the medieval period. In consequence, the chronological range of prehistoric underwater finds extends from the Mousterian period through to the Late Iron Age. Known sites currently number 33 in the SPLASHCOS Viewer with the greatest number belonging to the Neolithic or Bronze Age periods, but ongoing underwater surveys continue to add new sites to the list. Systematic research has intensified in the past decade and demonstrates the presence of in situ culture layers, excellent conditions of preservation including wooden remains in many cases, and the presence of artificial structures of stone and wood possibly built as protection against sea-level rise or as fish traps. Existing discoveries demonstrate the scope for new research and new discoveries and the integration of archaeological investigations with palaeoenvironmental and palaeoclimatic analyses of submerged sediments in lakes and on the seabed. A major challenge for the future is to develop better procedures for the integration of scientific research, commercial and industrial development, and the management and protection of the underwater heritage