Population Density, Group Size or Something in Between: Effects of a Variable Social Structure on Parasite Transmission

Critical to our understanding of disease dynamics and effective disease control strategies is the relationship between host density and parasite transmission rates. To accurately describe this relationship, it is important to measure host density at the scale in which transmission is occurring. In social species, for example, transmission may be more related to group size than the population as a whole. But when aggregation patterns vary in size across space and time, our ability to quantify the density-transmission relationship may depend on measuring density somewhere in between population density and group size. To address this issue, we examined elk (Cervus elaphus) populations in western Wyoming that have been exposed to the bacteria (Brucella abortus) that causes brucellosis. We measured elk density at multiple scales ranging from population density to group size, and evaluated the functional relationship between density and brucellosis seroprevalence. Our study found that low elk density did not explain why Brucella had not effectively invaded several populations. However, in populations with multiple years of seropositive test results, the rates of increase in seroprevalence saturate with increasing elk density regardless of the density measure used. The different densities were poorly correlated with one another, and therefore high elk densities at broad scales did not guarantee high elk densities at fine scales, but both may be important to the transmission of Brucella. This suggests that reducing or altering elk density may not effectively reduce transmission

Imperfect Tests, Pervasive Pathogens, and Variable Demographic Performance: Thoughts on Managing Bighorn Sheep Respiratory Disease

Respiratory disease (pneumonia) has been a persistent challenge for bighorn sheep (Ovis canadensis) conservation and its cause has been attributed to numerous bacteria including Mycoplasma ovipneumoniae and several Pasteurellaceae family species. This study sought to investigate efficacy of diagnostic protocols in detecting Pasteurellaceae and Mycoplasma ovipneumoniae, generate sampling recommendations for different protocols, assess the distribution of these disease agents among 17 bighorn sheep populations in Montana and Wyoming, and evaluate what associations existed between detection of these agents and demographic performance of bighorn sheep populations. Analysis of replicate samples from individual bighorn sheep revealed that detection probability for regularlyused diagnostic protocols was generally low (<50%) for Pasteurellaceae and was high (>70%) for Mycoplasma ovipneumoniae, suggesting that routine pathogen sampling likely mischaracterizes respiratory pathogen communities. Power analyses found that most pathogen species could be detected with 80% confidence at the population-level by conducting regularly-used protocols multiple times per animal. Each pathogen species was detected in over half of the study populations, but after accounting for detection probability there was low confidence in negative test results for populations where Pasteurellaceae species were not detected. Seventy-six percent of study populations hosted both Mycoplasma ovipneumoniae and Pasteurellaceae pathogens, yet a number of these populations were estimated to have positive population growth rates and recruitment rates greater than 30%. Overall, the results of this work suggest that bighorn sheep respiratory disease may be mitigated by manipulating population characteristics and respiratory disease epizootics could be caused by pathogens already resident in bighorn sheep population

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival