Seroprevalence and Associated Risk Factors of Infectious Bronchitis Virus in Chicken in Northwest Ethiopia.

Avian infectious bronchitis virus is a highly contagious disease occurring in respiratory, urogenital, and reproductive tissues of chicken causing considerable losses due to death, egg drop, and reduced production. This preliminary study was conducted to investigate the prevalence of antibodies against infectious bronchitis virus (IBV) and to assess the potential risk factors in chickens of northwest Ethiopia. A cross-sectional study was conducted from November 2020 to June 2021. A total of 768 serum samples from three zones were collected. To investigate the presence of antibodies against IBV, the indirect ELISA serological test was applied. Positivity for anti-IBV antibodies was observed in 23.96% (95% CI: 20.98-27.14) of the samples. The mixed-effect logistic regression analysis of potential risk factors showed that IBV prevalence was significantly higher in young chickens than adults (p < 0.001) and higher in intensive farm type than in extensive type (p < 0.001). Based on the production purposes of the chickens, the odds of seropositivity for IB was significantly higher in layers than in broilers (p < 0.001) and dual purposes (p < 0.001). This study revealed higher seroprevalence in farms which had the "all-in-all-out" rearing method than in farms with different batches in one house with a significant difference (p < 0.001), higher seroprevalence in the poor ventilated type than in good ones (p < 0.001), and higher seroprevalence in the houses that did not remove used litter at all than houses of completely disposed and partially disposed litter (p=0.002). Moreover, disinfection of houses had significant effect on the occurrence of IB. Having personal protective equipment was significantly affecting the occurrence of IB, being higher in the farms that have no wearing clothes and shoe than in those having wearing clothes and shoe (p=0.002). In conclusion, the seroprevalence finding in the present study indicated that the organism is circulating among the population of chickens and high enough to cause significant economic losses Therefore, poultry houses should be cleaned, disinfected, and well ventilated and farm attendants should have separate farm shoe and clothes. Further studies on the virus isolation and molecular characterization of the target gene are needed in the study area.

Mechanistic Projection of First-in-Human Dose for Bispecific Immunomodulatory P-Cadherin LP-DART: An Integrated PK/PD Modeling Approach.

A bispecific immunomodulatory biotherapeutic molecule (P-cadherin LP-DART) based on the Dual Affinity Re-Targeting (DART) scaffold has been developed as a potential antitumor treatment showing efficacy in preclinical testing. A minimal anticipated biological effect level (MABEL) approach was applied to project the first-in-human (FIH) dose, because of its immune agonistic properties following target engagement. The pharmacological activity of P-cadherin LP-DART is driven by binding to both P-cadherin on the tumor cells and CD3 on T cells. Therefore, the concentration of the tri-molecular synapse formed between drug, T cell, and tumor cell, rather than drug concentration, is responsible for efficacy. A mechanistic pharmacokinetic/pharmacodynamic (PK/PD)-driven approach was explored to understand the exposure-response relationship based on the synapse concentration to project the MABEL dose. Orthogonal approaches including PK-driven and receptor occupancy calculations were also investigated. This study showcases the application of PK/PD modeling in immune-oncology, and could potentially be implemented for other bispecific biotherapeutics.

The -137G/C polymorphism of interleukin 18 promoter and risk of HIV-1 infection and its progression to AIDS.

A growing body of evidence suggests that host genetic factors play an important role both in susceptibility to human immunodeficiency virus 1 (HIV-1) infection and in progression to AIDS. Interleukin 18 (IL-18) is a pleiotropic proinflammatory cytokine that serves as an important regulator of immune responses. It plays a key role in induction of both Th1 and Th2 cytokines and, thereby, modulates their immune responses. Single nucleotide polymorphisms in the IL-18 gene promoter region may lead to an altered transcriptional activity and IL-18 production, and so this may account for individuals' variation to the risk of HIV-1 infection. With this perspective, the -137G/C polymorphism in the promoter region of the IL-18 gene was studied in 500 patients with HIV-1/AIDS and an equal number of sex and age matched healthy controls using sequence specific polymerase chain reaction analysis. We did not observe any significant association of the heterozygous G/C genotype with the risk of HIV-1-infection/AIDS. However, statistically significant associations of the G allele and homozygous G/G genotype of -137 G/C polymorphism of IL-18 promoter with increased risk of HIV-1/AIDS were identified. The data of the present study suggest that IL-18 -137 G allele and G/G genotype seem to be involved in the pathogenesis of HIV-1 infection among North Indians.

IL-18 Gene Promoter Region 607C/A Polymorphism in HIV-1 Infected North Indian Population.

Several host genetic factors play an important role in susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and in its progression to acquired immune deficiency syndrome (AIDS). The interleukin-18 (IL-18) is a multifunctional proinflammatory cytokine that regulates immune responses and plays a pathogenic role in HIV-1 infection by enhancing viral replication. Single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter region may lead to altered transcriptional activity and IL-18 production, and may account for variation in the risk of HIV-1 infection. We have investigated the association between IL-18 promoter polymorphism -607C>A and HIV-1 infection through a case-control study of 500 patients with HIV-1/AIDS and an equal number of age and sex matched controls in a north Indian population. Genotyping using sequence specific primer-polymerase chain reaction (SSP-PCR) showed a statistically significant reduced risk of HIV-1 infection for the A>A genotype [odds ratio (OR) = 0.57, 95% confidence interval (95% CI) = 0.33-0.98, p = 0.040], but not for the C>A genotype (OR = 0.87, 95% CI = 0.66-1.14, p = 0.321). We concluded that the -607A allele of the IL-18 gene promoter polymorphism may play a protective role against the progression of HIV-1 infection in this population.

The influence of variations in the DNA repair (XRCC1) gene on HIV-1/AIDS among Indian population.

Genetic polymorphisms in DNA repair genes may influence individual variations in the DNA repair capacity. Polymorphisms in the XRCC1 gene that cause amino acid substitutions may impair the interaction of its proteins (XRCC1) with the other enzymatic proteins and consequently alter DNA repair function, which may be associated with the risk of HIV-1/AIDS disease. In this study, we aimed to determine the frequency of polymorphisms in XRCC1 codon 399 in a sample of Indian population with HIV-1/AIDS to evaluate its association with the disease. Polymerase chain reaction and restriction fragment length polymorphism were used to analyse XRCC1 Arg399Gln polymorphisms in 300 positively diagnosed cases with HIV-1/AIDS and an equal number of negatively diagnosed controls of the matched age. The XRCC1 homozygous variant genotype Gln399Gln was associated with an increased risk of HIV-1/AIDS disease (OR = 1.8, 95% CI 1.10-2.94), while no association was found with the Arg399Gln genotype. Polymorphisms in the XRCC1 homozygous variant genotype for the 399Gln allele were associated with the risk of HIV-1/AIDS disease in a sample of North Indian population.