Serosurvey of human antibodies recognizing Aedes aegypti D7 salivary proteins in Colombia

Citation: Londono-Renteria, B. L., Shakeri, H., Rozo-Lopez, P., Conway, M. J., Duggan, N., Jaberi-Douraki, M., & Colpitts, T. M. (2018). Serosurvey of Human Antibodies Recognizing Aedes aegypti D7 Salivary Proteins in Colombia. Frontiers in Public Health, 6. https://doi.org/10.3389/fpubh.2018.00111Background: Dengue is one of the most geographically significant mosquito-borne viral diseases transmitted by Aedes mosquitoes. During blood feeding, the mosquito deposits salivary proteins that induce antibody responses. These can be related to the intensity of exposure to bites. Some mosquito salivary proteins, such as D7 proteins, are known as potent allergens. The antibody response to D7 proteins can be used as a marker to evaluate the risk of exposure and disease transmission, and provide critical information for understanding the dynamics of vector-host interactions. Methods: The study was conducted at the Los Patios Hospital, Cucuta, Norte de Santander, Colombia. A total of 63 participants were enrolled in the study. Participants were categorized into three disease status groups, age groups, and socioeconomic strata. The level of IgG antibodies against D7 Aedes proteins was determined by ELISA. We used a statistical approach to determine if there is an association between antibody levels and factors such as age, living conditions, and dengue virus infection. Results: We found that IgG antibodies against D7 proteins were higher in non-DENV infected individuals in comparison to DENV-infected participants. Also, age factor showed a significant positive correlation with IgG antibodies against D7 proteins, and the living conditions (socioeconomic stratification), in people ages 20 years or older, are a statistically significant factor in the variability of IgG antibodies against D7 proteins. Conclusions: This pilot study represents the first approximation to elucidate any correlation between the antibody response against mosquito D7 salivary proteins and its correlation with age, living conditions and dengue virus infection in a dengue endemic area

Development of a subcutaneous ear implant to deliver an anaplasmosis vaccine to dairy steers

Bovine anaplasmosis is the most prevalent tick-transmitted disease of cattle worldwide and a major obstacle to profitable beef production. Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emergence of antimicrobial resistance in bacteria that may pose a risk to human health. Furthermore, the absence of effectiveness data for a commercially available, conditionally licensed anaplasmosis vaccine is a major impediment to implementing anaplasmosis control programs. The primary objective of this study was to develop a single-dose vaccine delivery platform to produce long-lasting protective immunity against anaplasmosis infections. Twelve Holstein steers, aged 11-12 weeks, were administered a novel 3-stage, single-dose vaccine against Anaplasma marginale (Am) major surface protein 1a. The vaccine consisted of a soluble vaccine administered subcutaneously (s.c.) for immune priming, a vaccine depot of a biodegradable polyanhydride rod with intermediate slow release of the vaccine for boosting immune response, and an immune-isolated vaccine platform for extended antigen release (VPEAR implant) deposited s.c. in the ear. Six calves were randomly assigned to two vaccine constructs (n=3) that featured rods and implants containing a combination of two different adjuvants, diethylaminoethyl (DEAE)-Dextran and Quil-A (Group A). The remaining 6 calves were randomly assigned to two vaccine constructs (n=3) that featured rods and implants containing the same adjuvant (either DEAE-Dextran or Quil A) (Group B). Twenty one months post-implantation, calves were challenged intravenously with Am stabilate and were monitored weekly for signs of fever, decreased packed cell volume (PCV) and bacteremia. Data were analyzed using a mixed effects model and chi-squared tests (SAS v9.04.01, SAS Institute, Cary, NC). Calves in Group A had higher PCV than calves in Group B (P = 0.006) at day 35 post-infection. Calves in Group A were less likely to require antibiotic intervention compared with calves in Group B (P = 0.014). Results indicate that calves exhibited diminished clinical signs of anaplasmosis when antigen was delivered with a combination of adjuvants as opposed to a single adjuvant. This demonstrates the feasibility of providing long lasting protection against clinical bovine anaplasmosis infections using a subcutaneous ear implant vaccine construct

Evaluation of Precision Livestock Technology and Human Scoring of Nursery Pigs in a Controlled Immune Challenge Experiment

The objectives were to determine the sensitivity, specificity, and cutoff values of a visual-based precision livestock technology (NUtrack), and determine the sensitivity and specificity of sickness score data collected with the live observation by trained human observers. At weaning, pigs (n = 192; gilts and barrows) were randomly assigned to one of twelve pens (16/pen) and treatments were randomly assigned to pens. Sham-pen pigs all received subcutaneous saline (3 mL). For LPS-pen pigs, all pigs received subcutaneous lipopolysaccharide (LPS; 300 µg/kg BW; E. coli O111:B4; in 3 mL of saline). For the last treatment, eight pigs were randomly assigned to receive LPS, and the other eight were sham (same methods as above; half-and-half pens). Human data from the day of the challenge presented high true positive and low false positive rates (88.5% sensitivity; 85.4% specificity; 0.871 Area Under Curve, AUC), however, these values declined when half-and-half pigs were scored (75% sensitivity; 65.5% specificity; 0.703 AUC). Precision technology measures had excellent AUC, sensitivity, and specificity for the first 72 h after treatment and AUC values were \u3e0.970, regardless of pen treatment. These results indicate that precision technology has a greater potential for identifying pigs during a natural infectious disease event than trained professionals using timepoint sampling

Predicting the Prognostic Value of <i>POLI</i> Expression in Different Cancers via a Machine Learning Approach

Translesion synthesis (TLS) is a cell signaling pathway that facilitates the tolerance of replication stress. Increased TLS activity, the particularly elevated expression of TLS polymerases, has been linked to resistance to cancer chemotherapeutics and significantly altered patient outcomes. Building upon current knowledge, we found that the expression of one of these TLS polymerases (POLI) is associated with significant differences in cervical and pancreatic cancer survival. These data led us to hypothesize that POLI expression is associated with cancer survival more broadly. However, when cancers were grouped cancer type, POLI expression did not have a significant prognostic value. We presented a binary cancer random forest classifier using 396 genes that influence the prognostic characteristics of POLI in cervical and pancreatic cancer selected via graphical least absolute shrinkage and selection operator. The classifier was then used to cluster patients with bladder, breast, colorectal, head and neck, liver, lung, ovary, melanoma, stomach, and uterus cancer when high POLI expression was associated with worsened survival (Group I) or with improved survival (Group II). This approach allowed us to identify cancers where POLI expression is a significant prognostic factor for survival (p = 0.028 in Group I and p = 0.0059 in Group II). Multiple independent validation approaches, including the gene ontology enrichment analysis and visualization tool and network visualization support the classification scheme. The functions of the selected genes involving mitochondrial translational elongation, Wnt signaling pathway, and tumor necrosis factor-mediated signaling pathway support their association with TLS and replication stress. Our multidisciplinary approach provides a novel way of identifying tumors where increased TLS polymerase expression is associated with significant differences in cancer survival

Dependence of T-cell waves, caused by the transience of the autoimmune state , on T-cell avidity and killing efficacy.

<p>The duration of T-cell waves for are plotted as a function of the parametric quantity , representing T-cell avidity, at the following values of T-cell killing efficacies : (solid line), (dashed line), (dotted line) and (dashed-dotted line) (day cell)⁻¹. These curves are all steadily decreasing functions of and vanish at (.</p

Heat-map simulations of the (scaled) two-clone model (S1.35)–(S1.40) showing the effects of varying T-cell avidity and killing efficacy on autoantibody predictability and detectability.

<p>The scaled level of -cells at steady state (A1–A4), the total scaled levels of autoreactive autoantibodies at the three time points: six months after the start of the autoimmune attack (B1–B4), at disease onset for those that develop the disease (C1–C4) and at steady state (D1–D4), and the time duration (in days) for (E1–E4) and (F1–F4) to reach the detectability level of , are simulated in response to variations to both T-cell avidity within the ranges (A1–F1), (A2–F2) (A3–F3) and (A4–F4), where inequality (2) is satisfied, and T-cell killing efficacy within the range (day cell)⁻¹. The black line in each panel represents the 30% threshold of surviving -cells (0.3-critical threshold), and the colors represent the levels of these quantities according to the color-bars on top of each column.</p

Predictive Models of Type 1 Diabetes Progression: Understanding T-Cell Cycles and Their Implications on Autoantibody Release

<div><p>Defining the role of T-cell avidity and killing efficacy in forming immunological response(s), leading to relapse-remission and autoantibody release in autoimmune type 1 diabetes (T1D), remains incompletely understood. Using competition-based population models of T- and B-cells, we provide a predictive tool to determine how these two parametric quantities, namely, avidity and killing efficacy, affect disease outcomes. We show that, in the presence of T-cell competition, successive waves along with cyclic fluctuations in the number of T-cells are exhibited by the model, with the former induced by transient bistability and the latter by transient periodic orbits. We hypothesize that these two immunological processes are responsible for making T1D a relapsing-remitting disease within prolonged but limited durations. The period and the number of peaks of these two processes differ, making them potential candidates to determine how plausible waves and cyclic fluctuations are in producing such effects. By assuming that T-cell and B-cell avidities are correlated, we demonstrate that autoantibodies associated with the higher avidity T-cell clones are first to be detected, and they reach their detectability level faster than those associated with the low avidity clones, independent of what T-cell killing efficacies are. Such outcomes are consistent with experimental observations in humans and they provide a rationale for observing rapid and slow progressors of T1D in high risk subjects. Our analysis of the models also reveals that it is possible to improve disease outcomes by unexpectedly increasing the avidity of certain subclones of T-cells. The decline in the number of -cells in these cases still occurs, but it terminates early, leaving sufficient number of functioning -cells in operation and the affected individual asymptomatic. These results indicate that the models presented here are of clinical relevance because of their potential use in developing predictive algorithms of rapid and slow progression to clinical T1D.</p></div