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COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of myocarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

Increasing antibiotic resistance is a matter of grave concern for consumers, public health authorities, farmers, and researchers. Antimicrobial peptides (AMPs) are emerging as novel and effective non-antibiotic tools to combat infectious diseases in poultry. In this study, we evaluated six avian AMPs including 2 truncated cathelicidins, [CATH-1(6–26) and CATH-2(1–15)], and 4 avian β-defensins (ABD1, 2, 6 and 9) for their bactericidal and immunomodulatory activities. Our findings have shown CATH-1(6–26) and ABD1 being the two most potent avian AMPs effective against Gram-positive and Gram-negative bacteria investigated in these studies. Moreover, CATH-1(6–26) inhibited LPS-induced NO production and exhibited dose-dependent cytotoxicity to HD11 cells. While, ABD1 blocked LPS-induced IL-1β gene induction and was non-toxic to HD11 cells. Importantly, in ovo administration of these AMPs demonstrated that ABD1 can offer significant protection from early chick mortality (44% less mortality in ABD1 treated group versus the control group) due to the experimental yolk sac infection caused by avian pathogenic Escherichia coli . Our data suggest that in ovo administration of ABD1 has immunomodulatory and anti-infection activity comparable with CpG ODN. Thus, ABD1 can be a significant addition to potential alternatives to antibiotics for the control of bacterial infections in young chicks.

Infant’s immune system cannot control infection or respond to vaccination as efficiently as older individuals, a phenomenon that has been attributed to immunological immaturity. Recently, we challenged this notion and proposed the presence of actively immunosuppressive and physiologically enriched CD71 + erythroid cells in neonates. Here we utilized Bordetella pertussis , a common neonatal respiratory tract pathogen, as a proof of concept to investigate the role of these cells in adaptive immunity. We observed that CD71 + cells have distinctive immunosuppressive properties and prevent recruitment of immune cells to the mucosal site of infection. CD71 + cells ablation unleashed induction of B. pertussis -specific protective cytokines (IL-17 and IFN-γ) in the lungs and spleen upon re-infection or vaccination. We also found that CD71 + cells suppress systemic and mucosal B. pertussis -specific antibody responses. Enhanced antigen-specific adaptive immunity following CD71 + cells depletion increased resistance of mice to B. pertussis infection. Furthermore, we found that human cord blood CD71 + cells also suppress T and B cell functions in vitro . Collectively, these data provide important insight into the role of CD71 + erythroid cells in adaptive immunity. We anticipate our results will spark renewed investigation in modulating the function of these cells to enhance host defense to infections in newborns.

Gamma-delta (γδ) T cells are a major immune cell subset in pigs. Approximately 50% of circulating T cells are γδ T cells in young pigs and up to 30% in adult sows. Despite this abundance, the functions of porcine γδ T cells are mostly unidentified. In humans and mice, activated γδ T cells exhibit broad innate cytotoxic activity against a wide variety of stressed, infected, and cancerous cells through death receptor/ligand-dependent and perforin/granzyme-dependent pathways. However, so far, it is unknown whether porcine γδ T cells have the ability to perform cytotoxic functions. In this study, we conducted a comprehensive phenotypic characterization of porcine γδ T cells isolated from blood, lung, and nasal mucosa. To further analyze the cytolytic potential of γδ T cells, cytotoxicity assays were performed using purified γδ T cells as effector cells and virus-exposed or mock-treated primary porcine alveolar macrophages as target cells. Our results show that only CD2 γδ T cells express cytotoxic markers (CD16, NKp46, perforin) with higher perforin and NKp46 expression in γδ T cells isolated from lung and nasal mucosa. Moreover, we found that γδ T cells can exhibit cytotoxic functions in a cell-cell contact and degranulation-dependent manner. However, porcine γδ T cells did not seem to specifically target Porcine Reproductive and Respiratory Syndrome Virus or swine Influenza A Virus-infected macrophages, which may be due to viral escape mechanisms. Porcine γδ T cells express cytotoxic markers and can exhibit cytotoxic activity in vitro. The specific mechanisms by which porcine γδ T cells recognize target cells are not fully understood but may involve the detection of cellular stress signals.

Many social, cultural, and systemic challenges affect the uptake of measles immunisation services. Prior studies have looked at the caregivers' perspectives, but little is known about the perspectives of the health care providers on the barriers of measles immunisation services in Canada. This study examined measles immunisation coverage trends across the regional health authorities in Saskatchewan and explored the barriers and enablers to measles immunisation coverage from providers' perspectives. The study adopted an explanatory sequential mixed method. We utilized the entire population of 16,582 children under two years of age available in the Saskatchewan Immunisation Management System (SIMS) registry for 2002 and 2013 in aggregate format and interviewed 18 key informants in pre-determined two-stages in 2016 and 2017. The quantitative analysis was done with Joinpoint regression modelling, while the qualitative interview data was analyzed using hybrid inductive and deductive thematic approaches. There was a 16.89%-point increase in measles immunisation coverage in the province from 56.32% to 73.21% between 2002 and 2013. There was also a persistently higher coverage among the affluent (66.95% - 82.37%) than the most deprived individuals (45.79% - 62.60%) in the study period. The annual rate of coverage change was marginally higher among the most deprived (16.81%; and average annual percentage change (AAPC) 2.0, 95% CI 1.7-2.2) than among the affluent group (15.42% and AAPC 3.0; 95% CI 2.0-4.0). While access-related issues, caregivers' fears, hesitancy, anti-vaccination challenges, and resource limitations were barriers to immunisation, improving community engagement, service delivery flexibility, targeted social responses and increasing media role were found useful to address the uptake of measles and other vaccine-preventable diseases immunisation. There is low coverage and inequity in measles immunisation uptake in Saskatchewan from social and institutional barriers. Even though there is evidence of disparity reduction among the different groups, the barriers to increasing measles immunisation coverage have implications for the health of the socio-economically deprived groups, the healthcare system and other vaccination programs. There is a need to improve policy framework for community engagement, targeted programs, and public health discourse.

Many social, cultural, and systemic challenges affect the uptake of measles immunisation services. Prior studies have looked at the caregivers’ perspectives, but little is known about the perspectives of the health care providers on the barriers of measles immunisation services in Canada. This study examined measles immunisation coverage trends across the regional health authorities in Saskatchewan and explored the barriers and enablers to measles immunisation coverage from providers’ perspectives. The study adopted an explanatory sequential mixed method. We utilized the entire population of 16,582 children under two years of age available in the Saskatchewan Immunisation Management System (SIMS) registry for 2002 and 2013 in aggregate format and interviewed 18 key informants in pre-determined two-stages in 2016 and 2017. The quantitative analysis was done with Joinpoint regression modelling, while the qualitative interview data was analyzed using hybrid inductive and deductive thematic approaches. There was a 16.89%-point increase in measles immunisation coverage in the province from 56.32% to 73.21% between 2002 and 2013. There was also a persistently higher coverage among the affluent (66.95% - 82.37%) than the most deprived individuals (45.79% - 62.60%) in the study period. The annual rate of coverage change was marginally higher among the most deprived (16.81%; and average annual percentage change (AAPC) 2.0, 95% CI 1.7–2.2) than among the affluent group (15.42% and AAPC 3.0; 95% CI 2.0–4.0). While access-related issues, caregivers’ fears, hesitancy, anti-vaccination challenges, and resource limitations were barriers to immunisation, improving community engagement, service delivery flexibility, targeted social responses and increasing media role were found useful to address the uptake of measles and other vaccine-preventable diseases immunisation. There is low coverage and inequity in measles immunisation uptake in Saskatchewan from social and institutional barriers. Even though there is evidence of disparity reduction among the different groups, the barriers to increasing measles immunisation coverage have implications for the health of the socio-economically deprived groups, the healthcare system and other vaccination programs. There is a need to improve policy framework for community engagement, targeted programs, and public health discourse.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

Studies in mice showed that African Zika virus (ZIKV) strains cause more damage in embryos. These studies, however, were limited to the mouse-adapted African MR766 strain or infection at early gestation. Here, we compared infection of Asian and African strains in the fetal pig model at midgestation. Both strains caused fetal infection. ZIKV was detected in placenta, amniotic membrane, amniotic fluid, fetal blood, and brain. The African strain produced more vigorous in utero infection as represented by more efficient virus transmission between siblings, and higher viral loads in fetal organs and membranes. Infection with both strains was associated with reduced fetal brain weight and increased number of placental CD163-positive cells, as well as elevated in utero interferon alpha and cortisol levels. This is the first large animal model study which demonstrated that African strain of ZIKV, with no passage history in experimental animals, can cause persistent infection in fetuses and fetal membranes at midgestation. Our studies also suggest that similar to Asian strains, ZIKV of African lineage might cause silent pathology which is difficult to identify in deceptively healthy fetuses. The findings emphasize the need for further studies to highlight the impact of ZIKV heterogeneity on infection outcomes during pregnancy.

Background Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus infecting pigs of all ages with high morbidity and mortality among newborn piglets. Currently, there is no effective vaccine available to protect the pigs from PEDV. The N-terminal subunit of spike protein (S1) is responsible for virus binding to the cellular receptor and contains a number of neutralizing antibody epitopes. Thus, we expressed and produced recombinant S1 protein to protect newborn piglets by immunization of sows. Methods Affinity tagged PEDV S1 protein was expressed in a secretory form in yeast, insect and mammalian cells to identify the most suitable production system. Purified recombinant protein was analysed by SDS-PAGE, Western blot and deglycosylation assay. A pregnant sow was intramuscularly immunized three times with adjuvanted recombinant protein prior to farrowing. PEDV-specific immune responses in sera and colostrum of the sow and piglets were assayed by ELISA and virus neutralization assays. Piglets were challenged orally with PEDV, and clinical parameters were monitored for 6 days post-challenge. Results and conclusion Of three eukaryotic expression systems tested (yeast, insect-cell, and mammalian), expression by HEK-293 T cells gave the highest yield of protein that was N-glycosylated and was the most appropriate candidate for vaccination. Administration of the subunit vaccine in a sow resulted in induction of S1-specific IgG and IgA that were passively transferred to the suckling piglets. Also, high virus neutralization titres were observed in the serum of the vaccinated sow and its piglets. After PEDV challenge, piglets born to the vaccinated sow exhibited less severe signs of disease and significantly lower mortality compared to the piglets of a control sow. However, there were no significant differences in diarrhea, body weight and virus shedding. Thus, vaccination with S1 subunit vaccine failed to provide complete protection to suckling piglets after challenge exposure, and further improvements are needed for the development of a subunit vaccine that fully protects against PEDV infection.

Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions.