The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. METHODOLOGY/ PRINCIPAL FINDINGS: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. CONCLUSIONS/SIGNIFICANCE: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans

Tumor cell-derived Timp-1 is necessary for maintaining metastasis-promoting Met-signaling via inhibition of Adam-10.

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Population Dynamics, Relative Abundance, and Habitat Suitability of Adult Red Drum (Sciaenops ocellatus) in Nearshore Waters of the North-Central Gulf of Mexico

In the Gulf of Mexico, the red drum (Sciaenops ocellatus) is an immensely popular sportfish, yet the Gulf of Mexico stock is currently managed as data-limited in federal waters. The results of the federal stock assessment conducted in 2016 for Gulf of Mexico red drum were not recommended for providing management advice. Consequently, we sought to address data gaps highlighted in the assessment by producing up-to- date overall and sex-specific growth models, standardized indices of relative abundance, and predictions of habitat suitability and by updating estimates of natural mortality. Using a time series for the period of 2006–2018, we assigned ages of 0–36 years to 1178 red drum. A negative binomial generalized linear model including variables for year, depth, surface temperature, dissolved oxygen, and bottom salinity was used to standardize an index of relative abundance. Examination of catch per unit of effort revealed that adult red drum were significantly more abundant in state waters than in federal waters. These findings were explained by habitat suitability models, which were used to identify surface current velocity, surface temperature, and depth as the strongest predictors of relative abundance. The results of our investigation reveal that the adult spawning stock of red drum in the Gulf of Mexico is not fully protected by the catch moratorium in federal waters

Vaccine antigens modulate the innate response of monocytes to Al(OH)3.

Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level

The burnout-depression conundrum: investigating construct-relevant multidimensionality across four countries and four patient samples

This research seeks to contribute to the ongoing discussion about the distinctive nature of burnout and depression. In a first study, we relied on employee samples from four European countries (N = 5199; 51.27% women; Mage = 43.14). In a second study, we relied on a large sample of patients (N = 5791; 53.70% women; Mage = 39.54) who received a diagnosis of burnout, depressive episode, job strain, or adaptation disorder. Across all samples and subsamples, we relied on the bifactor exploratory structural equation modelling to achieve an optimal disaggregation of the variance shared across our measures of burnout and depression from the variance uniquely associated with each specific subscale included in these measures. Our results supported the value of this representation of participants’ responses, as well as their invariance across samples. More precisely, our results revealed a strong underlying global factor representing participants’ levels of psychological distress, as well as the presence of equally strong specific factors supporting the distinctive nature of burnout and depression. This means that, although both conditions share common ground (i.e. psychological distress), they are not redundant. Interestingly, our results also unexpectedly suggested that suicidal ideation might represent a distinctive core component of depression.publishedVersio

Run-Off Replication of Host-Adaptability Genes Is Associated with Gene Transfer Agents in the Genome of Mouse-Infecting Bartonella grahamii

The genus Bartonella comprises facultative intracellular bacteria adapted to mammals, including previously recognized and emerging human pathogens. We report the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most prevalent Bartonella species in wild rodents. Comparative genomics revealed that rodent-associated Bartonella species have higher copy numbers of genes for putative host-adaptability factors than the related human-specific pathogens. Many of these gene clusters are located in a highly dynamic region of 461 kb. Using hybridization to a microarray designed for the B. grahamii genome, we observed a massive, putatively phage-derived run-off replication of this region. We also identified a novel gene transfer agent, which packages the bacterial genome, with an over-representation of the amplified DNA, in 14 kb pieces. This is the first observation associating the products of run-off replication with a gene transfer agent. Because of the high concentration of gene clusters for host-adaptation proteins in the amplified region, and since the genes encoding the gene transfer agent and the phage origin are well conserved in Bartonella, we hypothesize that these systems are driven by selection. We propose that the coupling of run-off replication with gene transfer agents promotes diversification and rapid spread of host-adaptability factors, facilitating host shifts in Bartonella