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Firefighting water additives improve extinguishing efficiency in both urban and rural settings. The rate and size of forest fires has increased due to anthropogenic factors, making the use of the most efficient fighting tactics extremely relevant. There exists little ecotoxicological data available for many of the products in current use. The aim of this study is to assess the toxicity of firefighting additives currently used in Canada to a variety of aquatic and terrestrial species. Additionally, a deterministic risk assessment was conducted for both aquatic and terrestrial species based off environmentally relevant rates of application. Several of the firefighting water additives tested were found to pose risks to a variety of the species tested, whereas some products appeared to be relatively safe under the worse-case hypothetical scenarios. Mitacs accelerate and Fire Rein

BACKGROUND: The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. METHODS: In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. The primary outcome was ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs) measured yearly by ELISA compared with 1 month (ie, 28 days) after immunisation. We report GMCs up to 2 years (Geneva, Switzerland, including neutralising antibodies up to 6 months) and 1 year (Lambaréné, Gabon; Kilifi, Kenya) after vaccination and factors associated with higher antibody persistence beyond 6 months, according to multivariable analyses. Trials and the observational study were registered at ClinicalTrials.gov (Geneva: NCT02287480 and NCT02933931; Kilifi: NCT02296983) and the Pan-African Clinical Trials Registry (Lambaréné PACTR201411000919191). FINDINGS: Of 217 vaccinees from the original studies (102 from the Geneva study, 75 from the Lambaréné study, and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné, and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 44 (100%) of 44 participants who had been given a high dose (ie, 10-50 million pfu) of vaccine and who were seropositive at day 28 remained seropositive at 2 years, whereas 33 (89%) of 37 who had been given the low dose (ie, 300 000 pfu) remained seropositive for 2 years (p=0·042). In participants who had received a high dose, ZEBOV glycoprotein IgG GMCs decreased significantly between their peak (at 1-3 months) and month 6 after vaccination in Geneva (p0·05). Neutralising antibodies seem to be less durable, with seropositivity dropping from 64-71% at 28 days to 27-31% at 6 months in participants from the Geneva study. INTERPRETATION: Antibody responses to single-dose rVSV-ZEBOV vaccination are sustained across dose ranges and settings, a key criterion in countries where booster vaccinations would be impractical. FUNDING: The Wellcome Trust and Innovative Medicines Initiative 2 Joint Undertaking.

Introduction Multiple myeloma (MM) is the second most common hematological malignancy in Europe and the US. The median survival after diagnosis is approximately 4-5 years (Röllig et al The Lancet 2015), with recent improvement observed in younger (Kyle et al Expert Rev Hematol 2014) and older patients (Kumar et al Leukemia 2013). The improvement in outcomes of MM patients is largely due to the introduction of autologous stem cell transplant (ASCT) and novel treatments including proteasome inhibitors and immunomodulators. Norwegian guidelines state that the preferred frontline treatment for MM patients under 65-70 years old is ASCT, but this option may be limited by comorbidity. Here, we report results from a retrospective, non-interventional study using data collected at the MM registry at Oslo University Hospital (OUS), Norway. The aim was to describe patient and disease characteristics, overall survival (OS), and potential predictors of death for the study population in Norway. Methods The study period was from 1 Jan 2008 to 31 Dec 2015. Patients (n=169) aged 18 years or older at MM diagnosis and who were treated at OUS (ASCT or not) or in 1 of 5 regional hospitals (ASCT only, with ASCT received at OUS and other treatments received locally), during the study period, were included. Study entry was defined as date of MM diagnosis and follow-up started from study entry. End of follow-up occurred at the first of: end of study period, loss to follow-up, or death. Variables used were part of routine practice. Descriptive analysis was done at diagnosis for the overall population, for patients who received ASCT (n=100), and for those who did not receive ASCT at any time during the study period (n=69). At treatment line 1, Cox models were used to identify potential predictors for OS. Results In the study, 55.6% of patients were diagnosed with MM at OUS and 25 of those patients (14.8% of total population) received ASCT. Patients who did not receive ASCT were older and included a larger percentage of women than in the transplant cohort (mean age non-ASCT 73.1±11.2 with 55.1% women and for ASCT 55.5±6.7 years with 45.0% women). More MM patients were diagnosed with Bence Jones (BJ) (21.9% of patients) or IgG type myeloma (54.4% of patients) than IgA type (20.1% of patients) (Table 1). Of transplant patients, more were of International Staging System (ISS) stage I or stage II than stage III MM, though 35.0% of patients were of unknown stage. Most non-transplant patients had unknown ISS stage, followed by stages II and III and the least number of patients were of stage I. Of the CRAB symptoms at diagnosis, most ASCT patients showed no hypercalcemia (80.0%), no renal impairment (90.0%), or no anemia (68.0%), and 34.0% presented with skeletal destruction (Table 1). Similarly, most non-transplant patients had no hypercalcemia (87.0%) and no renal impairment (79.7%) at diagnosis. Anemia and skeletal destruction were not measured in 24.6% of non-transplant patients. Of those with recorded results, more non-transplant patients had skeletal destruction than not and approximately the same number of non-transplant patients presented with anemia than not. High-risk cytogenic abnormalities, a criterion of the revised (R)-ISS, was unknown for most patients (80.5%). Median OS from start of treatment line 1 was 75.93 (90% confidence interval (CI): 68.23 to not reached) months for transplant patients and 34.20 (90% CI: 25.57-42.16) months for non-transplant patients. Variables including age group, sex, CRAB symptoms at diagnosis, type of first therapy, and type of MM at diagnosis were included in the Cox models per cohort, if they had a missingness of Conclusions For MM patients in Norway, overall survival was much greater for patients receiving transplant in the first line. Hypercalcemia at diagnosis predicted death for both transplant and non-transplant cohorts and anemia at diagnosis was identified as a decreased risk of death for transplant patients, but not well-recorded for non-transplant patients. Belonging to an older age group (>71 or 80 years old) also was a significant predictor of death, but only for non-transplant patients. Disclosures Schjesvold: Oncopeptides: Consultancy; Celgene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Honoraria; Bayer: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria; Novartis: Honoraria. Jenna:Janssen-Cilag: Other: Employee of StatFinn & EPID Research, contracted by Janssen-Cilag. Sõnajalg:Janssen-Cilag: Other: Employee of StatFinn & EPID Research, contracted by Janssen-Cilag. Leval:Janssen-Cilag: Employment. Rana:Janssen-Cilag: Employment. Castren-Kortekangas:Janssen-Cilag: Employment. Borgsten:Janssen-Cilag: Employment.

Bluetongue virus (BTV) causes the primarily vector-borne bluetongue disease of ruminants, which poses a permanent threat to Europe since new serotypes and strains are frequently introduced. Vaccination of cattle is essential to control BTV outbreaks. Commercial attenuated and inactivated vaccines are efficacious in reducing BTV spread and disease, but do not fulfil all safety, adaptability, or production requirements. Additionally, no current vaccines allow the differentiation of infected from vaccinated animals (DIVA). DIVA vaccines enable surveillance of BTV epidemiology and vaccine efficacy, and facilitate a quick return for countries to a BTV-free status. This thesis presents the development and evaluation of a novel subunit DIVA vaccine against BTV serotype 8 (BTV-8) in cattle. Five His-tagged recombinant BTV proteins (VP2, VP5 of BTV-8; NS1, NS2, NS3 of BTV-2) were produced in baculovirus or E. coli expression systems. Purification protocols were optimized for all but VP5. Based on the feasibility of protein production and the capability of the remaining four proteins to induce humoral or cellular immune responses in mice, VP2, NS1, and NS2 were selected to formulate an experimental vaccine combined to an ISCOM-matrix adjuvant (SubV). Next, cattle were immunized twice at a three-week interval with SubV, a commercial inactivated vaccine, or a placebo. SubV induced humoral immune responses, including virus-neutralizing antibodies, against all three proteins, as well as a cellular immune response directed against NS1. These responses were of similar type and comparable magnitude between both vaccines, suggesting that SubV might provide protection that is at least as effective as the commercial vaccine. Finally, the protective efficacy of SubV was evaluated and complete virological and clinical protection against virulent BTV-8 challenge was observed following vaccination in calves. This was likely due to the induction of virus-neutralizing antibodies directed against VP2 of BTV-8 and cross-serotype T cell responses directed against NS1 and NS2 of BTV-2. Furthermore, SubV was shown to be DIVA-compliant based on the detection of antibodies directed against VP7, by using commercially-available diagnostic assays. This novel BTV subunit vaccine is a promising candidate and should be further developed.

Session 3 : Antivirals & Vaccines; The incursion and circulation of more than nine different serotypes of Bluetongue virus (BTV) in central and northern Europe over the past fifteen years has resulted in decreased animal welfare and production losses. Vaccination is crucial for controlling BTV since conventional biosecurity measures have limited impact on vector-borne diseases. However, as current vaccines have no accepted characteristic allowing for the differentiation of infected from vaccinated animals (DIVA), the use of these products impairs sero-epidemiological surveillance and thus a quick return to BTV-free status as well as serological monitoring of vaccine efficacy in the field. Small ruminants show the most severe clinical signs following BTV infection, but cattle are the virus’s main amplifying host and when infected with certain BTV strains, such as BTV-8, they can also display clinical signs. However, protective bovine immune responses against BTV are poorly characterized and there is limited information available about the ability of commercial and experimental vaccines to induce clinical and virological protection against BTV infection in cattle. Our objective was to develop and evaluate the efficacy of a novel DIVA subunit vaccine against BTV-8 in cattle, that later may be developed into a multi-serotype vaccine. We produced recombinant VP2 of BTV-8 and NS1 and NS2 of BTV-2 and formulated the vaccine with the purified proteins and an ISCOM-based adjuvant (SubV). The DIVA characteristic of this vaccine is based on the detection of VP7 antibodies in infected animals, thereby enabling the detection of BTV infection of any serotype. In the first study, we evaluated the immunogenicity of SubV in comparison with a commercial inactivated vaccine against BTV-8. Cows were subcutaneously immunized twice at a 3-weeks interval with SubV (n=5), the commercial vaccine (n=5), or with placebo (n=5). Humoral and cell-mediated immune responses were monitored before each vaccination as well as at 3 and 6 weeks after the second immunization. Both vaccines induced similar serum neutralizing antibody titers and the specific IgG1 antibody responses detected against VP2, NS1, and NS2 were strongest in cows immunized with SubV. Furthermore, serotype cross-reactive humoral and cell-mediated immunological responses to BTV-8 were detected to NS2 and NS1 of BTV-2, respectively. In the second study, calves were immunized twice at a 3-weeks interval with either SubV (n=6) or placebo (n=6), then challenged with BTV-8 three weeks later in a Biosecurity level 3 facility. Whereas controls developed strong viremia and clinical signs of Bluetongue disease including fever, mucosal congestion, and stiffness, vaccinated calves did not show any of these signs and were strongly protected against BTV infection. Preliminary data indicate that vaccinated animals developed very strong serum neutralizing antibody responses following vaccination. Humoral and cellular immunological analyses are ongoing and clinical, virological, and immunological results of both studies will be presented during the meeting. Taken together, these data indicate that our novel subunit DIVA vaccine composed of only three BTV proteins is very effective against BTV-8 infection in cattle, and will also enable serological monitoring of any BTV serotype in circulation in vaccinated populations. Furthermore, the serotype cross-reactivity of NS1 and NS2 suggests that this vaccine may be expanded in the future to target multiple BTV serotypes through the addition of purified recombinant VP2 of other serotypes.

Medicinsk entomologi