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1.
Reprod Toxicol ; 107: 69-80, 2022 01.
Article in English | MEDLINE | ID: covidwho-1531737

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people in a worldwide pandemic. A recently developed recombinant Plant-Derived Virus-Like Particle Vaccine candidate for COVID-19 (CoVLP) formulated with AS03 has been shown to be well-tolerated and highly immunogenic in healthy adults. Since the target population for the vaccine includes women of childbearing potential, the objective of the study was to evaluate any untoward prenatal and postnatal effects of AS03-adjuvanted CoVLP administered intramuscularly to Sprague-Dawley female rats before cohabitation for mating (22 and 8 days prior) and during gestation (Gestation Days [GD] 6 and 19). The embryo-fetal development (EFD) cohort was subjected to cesarean on GD 21 and the pre/post-natal (PPN) cohort was allowed to naturally deliver. Effects of AS03-adjuvanted CoVLP was evaluated on pregnant rats, embryo-fetal development (EFD), during parturition, lactation and the development of the F1 offspring up to weaning Vaccination with AS03-adjuvanted CoVLP induced an antibody response in F0 females and anti-SARS-CoV-2 spike-specific maternal antibodies were detected in the offspring at the end of the gestation and lactation periods. Overall, there was no evidence of untoward effects of AS03-adjuvanted CoVLP on the fertility or reproductive performance of the vaccinated F0 females. There was no evidence of untoward effects on embryo-fetal development (including teratogenicity), or early (pre-weaning) development of the F1 offspring. These results support the acceptable safety profile of the AS03-adjuvanted CoVLP vaccine for administration to women of childbearing potential.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Embryonic Development/drug effects , Fertility/drug effects , Fetal Development/drug effects , Polysorbates/administration & dosage , Squalene/administration & dosage , Vaccines, Virus-Like Particle/administration & dosage , alpha-Tocopherol/administration & dosage , Animals , Animals, Newborn , Antibodies, Viral/blood , Drug Combinations , Female , Immunoglobulin G/blood , Maternal-Fetal Exchange , Pregnancy , Rats, Sprague-Dawley , Recombinant Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Tobacco/genetics
2.
Sci Rep ; 11(1): 20715, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1479810

ABSTRACT

The current COVID-19 pandemic has created unmeasurable damages to society at a global level, from the irreplaceable loss of life, to the massive economic losses. In addition, the disease threatens further biodiversity loss. Due to their shared physiology with humans, primates, and particularly great apes, are susceptible to the disease. However, it is still uncertain how their populations would respond in case of infection. Here, we combine stochastic population and epidemiological models to simulate the range of potential effects of COVID-19 on the probability of extinction of mountain gorillas. We find that extinction is sharply driven by increases in the basic reproductive number and that the probability of extinction is greatly exacerbated if the immunity lasts less than 6 months. These results stress the need to limit exposure of the mountain gorilla population, the park personnel and visitors, as well as the potential of vaccination campaigns to extend the immunity duration.


Subject(s)
Ape Diseases/epidemiology , Ape Diseases/physiopathology , COVID-19/epidemiology , COVID-19/physiopathology , Animals , Animals, Newborn , COVID-19/veterinary , Computer Simulation , Endangered Species , Female , Gorilla gorilla , Immune System , Male , Models, Statistical , Pandemics , Probability , SARS-CoV-2 , Stochastic Processes
3.
Med Sci Monit ; 26: e922281, 2020 Mar 31.
Article in English | MEDLINE | ID: covidwho-1453382

ABSTRACT

BACKGROUND Acute respiratory distress syndrome (ARDS) is a sudden and serious disease with increasing morbidity and mortality rates. Phosphodiesterase 4 (PDE4) is a novel target for inflammatory disease, and ibudilast (IBU), a PDE4 inhibitor, inhibits inflammatory response. Our study investigated the effect of IBU on the pathogenesis of neonatal ARDS and the underlying mechanism related to it. MATERIAL AND METHODS Western blotting was performed to analyze the expression levels of PDE4, CXCR4, SDF-1, CXCR5, CXCL1, inflammatory cytokines, and proteins related to cell apoptosis. Hematoxylin-eosin staining was performed to observe the pathological morphology of lung tissue. Pulmonary edema score was used to assess the degree of lung water accumulation after pulmonary injury. Enzyme-linked immunosorbent assay (ELISA) was used to assess levels of inflammatory factors (TNF-alpha, IL-1ß, IL-6, and MCP-1) in serum. TUNEL assay was used to detect apoptotic cells. RESULTS Increased expression of PDE4 was observed in an LPS-induced neonatal ARDS mouse model, and IBU ameliorated LPS-induced pathological manifestations and pulmonary edema in lung tissue. In addition, IBU attenuated the secretion of inflammatory cytokines by inactivating the chemokine axis in the LPS-induced neonatal ARDS mouse model. Finally, IBU significantly reduced LPS-induced cell apoptosis in lung tissue. CONCLUSIONS IBU, a PDE4 inhibitor, protected against ARDS by interfering with pulmonary inflammation and apoptosis. Our findings provide a novel and promising strategy to regulate pulmonary inflammation in ARDS.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Inflammation/drug therapy , Phosphodiesterase 4 Inhibitors/pharmacology , Pyridines/pharmacology , Respiratory Distress Syndrome, Newborn/drug therapy , Animals , Animals, Newborn , Apoptosis/drug effects , Apoptosis/immunology , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Humans , Inflammation/diagnosis , Inflammation/immunology , Inflammation/pathology , Injections, Intraperitoneal , Lipopolysaccharides/immunology , Lung/drug effects , Lung/immunology , Lung/pathology , Mice , Phosphodiesterase 4 Inhibitors/therapeutic use , Pyridines/therapeutic use , Respiratory Distress Syndrome, Newborn/diagnosis , Respiratory Distress Syndrome, Newborn/immunology , Respiratory Distress Syndrome, Newborn/pathology , Signal Transduction/drug effects , Signal Transduction/immunology
4.
Mikrochim Acta ; 188(10): 352, 2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1432545

ABSTRACT

Extracellular ATP as a purinergic signaling molecule, together with ATP receptor, are playing an important role in tumor growth, therapy resistance, and host immunity suppression. Meanwhile ATP is a crucial indicator for cellular energy status and viability, thus a vital variable for tissue regeneration and in vitro tissue engineering. Most recent studies on COVID-19 virus suggest infection caused ATP deficit and release as a major characterization at the early stage of the disease and major causes for disease complications. Thus, imaging ATP molecule in both cellular and extracellular contexts has many applications in biology, engineering, and clinics. A sensitive and selective fluorescence "signal-on" probe for ATP detection was constructed, based on the base recognition between a black hole quencher (BHQ)-labeled aptamer oligonucleotide and a fluorophore (Cy5)-labeled reporter flare. The probe was able to detect ATP in solution with single digit µM detection limit. With the assistance of lipofectamine, this probe efficiently entered and shined in the model cells U2OS within 3 h. Further application of the probe in specific scenery, cardio-tissue engineering, was also tested where the ATP aptamer complex was able to sense cellular ATP status in a semi-quantitative manner, representing a novel approach for selection of functional cardiomyocytes for tissue engineering. At last a slight change in probe configuration in which a flexible intermolecular A14 linker was introduced granted regeneration capability. These data support the application of this probe in multiple circumstances where ATP measurement or imaging is on demand.


Subject(s)
Adenosine Triphosphate/analysis , Aptamers, Nucleotide , Carbocyanines , Fluorescent Dyes , Animals , Animals, Newborn , Cell Line , Fluorescence , Humans , Myocytes, Cardiac , Rats
5.
Cells ; 10(9)2021 09 09.
Article in English | MEDLINE | ID: covidwho-1408628

ABSTRACT

The present study sought to identify gene networks that are hallmarks of the developing inguinal subcutaneous adipose tissue (iWAT) and the interscapular brown adipose tissue (BAT) in the mouse. RNA profiling revealed that the iWAT of postnatal (P) day 6 mice expressed thermogenic and lipid catabolism transcripts, along with the abundance of transcripts associated with the beige adipogenesis program. This was an unexpected finding, as thermogenic BAT was believed to be the only site of nonshivering thermogenesis in the young mouse. However, the transcriptional landscape of BAT in P6 mice suggests that it is still undergoing differentiation and maturation, and that the iWAT temporally adopts thermogenic and lipolytic potential. Moreover, P6 iWAT and adult (P56) BAT were similar in their expression of immune gene networks, but P6 iWAT was unique in the abundant expression of antimicrobial proteins and virus entry factors, including a possible receptor for SARS-CoV-2. In summary, postnatal iWAT development is associated with a metabolic shift from thermogenesis and lipolysis towards fat storage. However, transcripts of beige-inducing signal pathways including ß-adrenergic receptors and interleukin-4 signaling were underrepresented in young iWAT, suggesting that the signals for thermogenic fat differentiation may be different in early postnatal life and in adulthood.


Subject(s)
Adipocytes, Beige/metabolism , Transcription, Genetic , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Animals , Animals, Newborn , Biomarkers/metabolism , Cell Cycle/genetics , Gene Expression Regulation, Developmental , Gene Ontology , Gene Regulatory Networks , Male , Mice, Inbred C57BL , Models, Biological , Muscle Development/genetics , Neuropeptides/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction
6.
J Cell Mol Med ; 25(17): 8558-8566, 2021 09.
Article in English | MEDLINE | ID: covidwho-1393908

ABSTRACT

Mesenchymal stem cells (MSCs) have been shown as an effective medicinal means to treat bronchopulmonary dysplasia (BPD). The widely used MSCs were from Wharton's jelly of umbilical cord (UC-MSCs) and bone marrow (BM-MSCs). Amniotic fluid MSCs (AF-MSCs) may be produced before an individual is born to treat foetal diseases by autoplastic transplantation. We evaluated intratracheal (IT) MSCs as an approach to treat an hyperoxia-induced BPD animal model and compared the therapeutic effects between AF-, UC- and BM-MSCs. A BPD animal model was generated by exposing newborn rats to 95% O2 . The continued stress lasted 21 days, and the treatment of IT MSCs was conducted for 4 days. The therapeutic effects were analysed, including lung histology, level of inflammatory cytokines, cell death ratio and state of angiogenesis, by sacrificing the experimental animal at day 21. The lasting hyperoxia stress induced BPD similar to the biological phenotype. The treatment of IT MSCs was safe without deaths and normal organ histopathology. Specifically, the treatment was effective by inhibiting the alveolar dilatation, reducing inflammatory cytokines, inducing angiogenesis and lowering the cell death ratio. AF-MSCs had better therapeutic effects compared with UC-MSCs in relieving the pulmonary alveoli histological changes and promoting neovascularization, and UC-MSCs had the best immunosuppressive effect in plasma and lung lysis compared with AF-MSCs and BM-MSCs. This study demonstrated the therapeutic effects of AF-, UC- and BM-MSCs in BPD model. Superior treatment effect was provided by antenatal MSCs compared to BM-MSC in a statistical comparison.


Subject(s)
Bronchopulmonary Dysplasia/therapy , Hyperoxia/therapy , Mesenchymal Stem Cell Transplantation/methods , Animals , Animals, Newborn , Cells, Cultured , Humans , Mesenchymal Stem Cells , Neovascularization, Physiologic , Rats , Rats, Sprague-Dawley , Umbilical Cord
7.
Mol Ther ; 29(10): 3042-3058, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1331299

ABSTRACT

Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail, termed 7G-modRNA, of four cardiac-reprogramming genes-Gata4 (G), Mef2c (M), Tbx5 (T), and Hand2 (H)-together with three reprogramming-helper genes-dominant-negative (DN)-TGFß, DN-Wnt8a, and acid ceramidase (AC)-to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Through a lineage-tracing model, we determined that delivering the 7G-modRNA cocktail at the time of myocardial infarction reprogrammed ∼25% of CM-like cells in the scar area and significantly improved cardiac function, scar size, long-term survival, and capillary density. Mechanistically, we determined that while 7G-modRNA cannot create de novo beating CMs in vitro or in vivo, it can significantly upregulate pro-angiogenic mesenchymal stromal cells markers and transcription factors. We also demonstrated that our 7G-modRNA cocktail leads to neovascularization in ischemic-limb injury, indicating CM-like cells importance in other organs besides the heart. modRNA is currently being used around the globe for vaccination against COVID-19, and this study proves this is a safe, highly efficient gene delivery approach with therapeutic potential to treat ischemic diseases.


Subject(s)
Cellular Reprogramming/genetics , Genetic Therapy/methods , Ischemia/therapy , Muscle, Skeletal/blood supply , Myocardial Infarction/therapy , Neovascularization, Physiologic/genetics , Regeneration/genetics , Transfection/methods , Animals , Animals, Newborn , Cells, Cultured , Disease Models, Animal , Female , Fibroblasts/metabolism , Humans , Male , Mice , Mice, Knockout, ApoE , Myocytes, Cardiac/metabolism , RNA, Messenger/genetics
8.
PLoS One ; 16(6): e0253543, 2021.
Article in English | MEDLINE | ID: covidwho-1282302

ABSTRACT

Based on several lines of evidence, numerous investigators have suggested that acetaminophen exposure during early development can induce neurological disorders. We had previously postulated that acetaminophen exposure early in life, if combined with antioxidants that prevent accumulation of NAPQI, the toxic metabolite of acetaminophen, might be innocuous. In this study, we administered acetaminophen at or below the currently recommended therapeutic dose to male laboratory rat pups aged 4-10 days. The antioxidants cysteine and mannitol were included to prevent accumulation of NAPQI. In addition, animals were exposed to a cassette of common stress factors: an inflammatory diet, psychological stress, antibiotics, and mock infections using killed bacteria. At age 37-49 days, observation during introduction to a novel conspecific revealed increased rearing behavior, an asocial activity, in animals treated with acetaminophen plus antioxidants, regardless of their exposure to oxidative stress factors (2-way ANOVA; P < 0.0001). This observation would suggest that the initial hypothesis is incorrect, and that oxidative stress mediators do not entirely eliminate the effects of acetaminophen on neurodevelopment. This study provides additional cause for caution when considering the use of acetaminophen in the pediatric population, and provides evidence that the effects of acetaminophen on neurodevelopment need to be considered both in the presence and in the absence of oxidative stress.


Subject(s)
Acetaminophen/pharmacology , Behavior, Animal/drug effects , Cysteine/pharmacology , Mannitol/pharmacology , Neurogenesis/drug effects , Animals , Animals, Newborn , Female , Male , Rats , Rats, Sprague-Dawley
9.
Sci Immunol ; 6(60)2021 06 15.
Article in English | MEDLINE | ID: covidwho-1270873

ABSTRACT

The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high magnitude IgG binding to RBD, N terminus domain, S1, and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4 and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines were well-tolerated and highly immunogenic in infant RMs, providing proof-of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Animals , Animals, Newborn , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , Macaca mulatta , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/immunology
10.
Neurobiol Dis ; 156: 105422, 2021 08.
Article in English | MEDLINE | ID: covidwho-1267874

ABSTRACT

Synthetic glucocorticoids (sGCs) such as dexamethasone (DEX), while used to mitigate inflammation and disease progression in premature infants with severe bronchopulmonary dysplasia (BPD), are also associated with significant adverse neurologic effects such as reductions in myelination and abnormalities in neuroanatomical development. Ciclesonide (CIC) is a sGC prodrug approved for asthma treatment that exhibits limited systemic side effects. Carboxylesterases enriched in the lower airways convert CIC to the glucocorticoid receptor (GR) agonist des-CIC. We therefore examined whether CIC would likewise activate GR in neonatal lung but have limited adverse extra-pulmonary effects, particularly in the developing brain. Neonatal rats were administered subcutaneous injections of CIC, DEX or vehicle from postnatal days 1-5 (PND1-PND5). Systemic effects linked to DEX exposure, including reduced body and brain weight, were not observed in CIC treated neonates. Furthermore, CIC did not trigger the long-lasting reduction in myelin basic protein expression in the cerebral cortex nor cerebellar size caused by neonatal DEX exposure. Conversely, DEX and CIC were both effective at inducing the expression of select GR target genes in neonatal lung, including those implicated in lung-protective and anti-inflammatory effects. Thus, CIC is a promising, novel candidate drug to treat or prevent BPD in neonates given its activation of GR in neonatal lung and limited adverse neurodevelopmental effects. Furthermore, since sGCs such as DEX administered to pregnant women in pre-term labor can adversely affect fetal brain development, the neurological-sparing properties of CIC, make it an attractive alternative for DEX to treat pregnant women severely ill with respiratory illness, such as with asthma exacerbations or COVID-19 infections.


Subject(s)
Cerebellum/drug effects , Cerebral Cortex/drug effects , Glucocorticoids , Lung/drug effects , Pregnenediones/pharmacology , Prodrugs/pharmacology , Signal Transduction/drug effects , Animals , Animals, Newborn , Anti-Inflammatory Agents/pharmacology , Body Weight/drug effects , Brain/drug effects , Brain/growth & development , COVID-19/drug therapy , Dexamethasone/pharmacology , Female , Mice , Mice, Inbred C57BL , Myelin Basic Protein/biosynthesis , Organ Size/drug effects , Pregnancy , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/drug effects
11.
Sci Rep ; 11(1): 371, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-1242035

ABSTRACT

Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. We were able to safely and effectively transfect the bronchial epithelium of foals using naked mRNA (i.e., mRNA formulated in a sodium citrate buffer without a delivery vehicle). Endoscopic examination of the bronchial tree and histology of mucosal biopsies indicated no gross or microscopic adverse effects of the transfection. Our data suggest that mRNA administered by an atomization device eliminates the need for chemical transfection agents, which can reduce the cost and the safety risks of delivering mRNA to the respiratory tract of animals and humans.


Subject(s)
Horses , Nasal Sprays , RNA, Messenger/administration & dosage , Respiratory Mucosa , Animals , Animals, Newborn , Cells, Cultured , Drug Carriers/administration & dosage , Drug Carriers/adverse effects , Drug Carriers/pharmacokinetics , Drug Delivery Systems/adverse effects , Drug Delivery Systems/methods , Drug Delivery Systems/veterinary , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Lung/drug effects , Lung/metabolism , Nebulizers and Vaporizers/veterinary , Polyethyleneimine/administration & dosage , Polyethyleneimine/chemistry , RNA, Messenger/adverse effects , RNA, Messenger/pharmacokinetics , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Transcription, Genetic , Transfection/methods , Transfection/veterinary , Vaccines, DNA/administration & dosage , Vaccines, DNA/adverse effects , Vaccines, DNA/pharmacokinetics
12.
Vet Immunol Immunopathol ; 237: 110254, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1239778

ABSTRACT

This study was performed to elucidate whether the route of booster vaccination affects the immune response against respiratory vaccine viruses in pre-weaning beef calves that receive primary intranasal (IN) vaccination during the first month of life. The objective was to compare the serum neutralizing antibody (SNA) titers to BHV1, BRSV, and BPI3V, cytokine mRNA expression and mucosal BHV1- and BRSV-specific IgA in nasal secretions following administration of IN or subcutaneous (SC) modified-live virus (MLV) booster vaccines 60 days after primary IN vaccination in young beef calves. Twenty-one beef calves were administered 2 mL of an IN MLV vaccine containing BHV1, BRSV, and BPI3V (Inforce3®) between one and five weeks of age. Sixty days after primary vaccination, calves were randomly assigned to one of two groups: IN-MLV (n = 11): Calves received 2 mL of the same IN MLV vaccine used for primary vaccination and 2 mL of a SC MLV vaccine containing BVDV1 & 2 (Bovi- Shield GOLD® BVD). SC-MLV (n = 10): Calves were administered 2 mL of a MLV vaccine containing, BHV1, BRSV, BPI3V, and BVDV1 & 2 (Bovi-Shield GOLD® 5). Blood and nasal secretion samples were collected on days -61 (primary vaccination), -28, -14, 0 (booster vaccination), 14, 21, 28, 42 and 60 for determination of SNA titers, cytokine gene expression analysis and nasal virus-specific IgA concentrations. Statistical analysis was performed using a repeated measures analysis through PROC GLIMMIX of SAS®. Booster vaccination by neither IN nor SC routes induced a significant increase in SNA titers against BHV1, BRSV, and BPI3V. Subcutaneous booster vaccination induced significantly greater BRSV-specific SNA titers (on day 42) and IgA concentration in nasal secretions (on days 21 and 42) compared to calves receiving IN booster vaccination. Both IN and SC booster vaccination were able to stimulate the production of BHV1-specific IgA in nasal secretions. In summary, booster vaccination of young beef calves using either SC or IN route two months after IN MLV primary vaccination resulted in comparable SNA titers, cytokine gene expression profile and virus-specific IgA concentration in nasal secretions. Only a few differences in the systemic and mucosal immune response against BHV1 and BRSV were observed. Subcutaneous booster vaccination induced significantly greater BRSV-specific SNA and secretory IgA titers compared to IN booster vaccination.


Subject(s)
Cattle Diseases/immunology , Respiratory Syncytial Virus Vaccines/immunology , Respiratory Syncytial Virus, Bovine/immunology , Administration, Intranasal/veterinary , Animals , Animals, Newborn , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cattle , Cattle Diseases/prevention & control , Cytokines/blood , Immunization, Secondary/veterinary , Immunogenicity, Vaccine , Respiratory Syncytial Virus Vaccines/administration & dosage
14.
Front Immunol ; 11: 597433, 2020.
Article in English | MEDLINE | ID: covidwho-983709

ABSTRACT

Newborns are highly susceptible to infectious diseases. The underlying mechanism of neonatal infection susceptibility has generally been related to their under-developed immune system. Nevertheless, this notion has recently been challenged by the discovery of the physiological abundance of immunosuppressive erythroid precursors CD71+ erythroid cells (CECs) in newborn mice and human cord blood. Here, as proof of concept, we show that these cells are also abundant in the peripheral blood of human newborns. Although their frequency appears to be more variable compared to their counterparts in mice, they rapidly decline by 4 weeks of age. However, their proportion remains significantly higher in infants up to six months of age compared to older infants. We found CD45 expressing CECs, as erythroid progenitors, were the prominent source of reactive oxygen species (ROS) production in both humans and mice. Interestingly, a higher proportion of CD45+CECs was observed in the spleen versus bone marrow of neonatal mice, which was associated with a higher ROS production by splenic CECs compared to their siblings in the bone marrow. CECs from human newborns suppressed cytokine production by CD14 monocytes and T cells, which was partially abrogated by apocynin in vitro. Moreover, the depletion of CECs in neonatal mice increased the number of activated effector immune cells in their spleen and liver, which rendered them more resistant to Listeria monocytogenes infection. This was evident by a significant reduction in the bacteria load in the spleen, liver and brain of treated-mice compared to the control group, which enhanced their survival rate. Our finding highlights the immunoregulatory processes mediated by CECs in newborns. Thus, such tightly regulated immune system in newborns/infants may explain one potential mechanism for the asymptomatic or mild COVID-19 infection in this population.


Subject(s)
Antigens, CD/immunology , Erythroid Precursor Cells , Listeria monocytogenes/immunology , Listeriosis , Receptors, Transferrin/immunology , Animals , Animals, Newborn , COVID-19/immunology , COVID-19/pathology , Erythroid Precursor Cells/immunology , Erythroid Precursor Cells/pathology , Erythroid Precursor Cells/transplantation , Female , Heterografts , Humans , Infant, Newborn , Listeriosis/immunology , Listeriosis/pathology , Listeriosis/therapy , Male , Mice , Mice, Inbred BALB C , SARS-CoV-2/immunology
15.
Comp Immunol Microbiol Infect Dis ; 73: 101567, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-885228

ABSTRACT

The etiology of neonatal diarrhea is multifactorial and remains one of the greatest health problems in sheep livestock farming. Faecal samples from 559 neonatal lambs aged less than 30 days from 30 sheepfolds located in the north-center region of Algeria were screened with pathogen-specific antigen ELISA for Cryptosporidium parvum, Escherichia coli K99, rotavirus, and coronavirus. Of the 559 lambs, 312 (58.81 %), 155 (27.72 %), 72 (12.88 %) and 20 (3.57 %) were positives for C. parvum, E. coli K99, rotavirus and coronavirus antigens, respectively. The prevalence of C. parvum was the highest (p < 0.0001). C. parvum, E. coli K99, rotavirus and coronavirus were observed in 23 (76.66 %), 17 (56.66 %), 9 (30 %) and 3 (10 %) sheepfolds, respectively. Compared to age, the prevalence of C. parvum was highest during the second and third week of age (p < 0.001). In contrast, other pathogens were found to be more frequent in lambs aged ≤7 days (p < 0.001). The number of lambs with diarrhea was 280 (50.09 %) of which 280 (100 %), 127 (45.35 %), 52 (18.57 %) and 10 (3.57 %) were found to be infected with C. parvum, E. coli K99, rotavirus and coronavirus, respectively (p < 0.0001). In various combinations, mixed infections were detected only with C. parvum. This is the first report of C. parvum, E. coli K99, rotavirus, and coronavirus in ≤30-days old neonatal lambs in Algeria. Special attention should be given to the first colostrum feeding, hygiene of the farm, prevention and control measures for a better prevention of neonatal diarrhea in lambs.


Subject(s)
Coronavirus Infections/veterinary , Cryptosporidiosis/epidemiology , Escherichia coli Infections/veterinary , Escherichia coli/classification , Rotavirus Infections/veterinary , Sheep Diseases/epidemiology , Algeria/epidemiology , Animals , Animals, Newborn , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cryptosporidium parvum , Escherichia coli Infections/epidemiology , Feces/microbiology , Feces/parasitology , Feces/virology , Rotavirus Infections/epidemiology , Sheep , Sheep Diseases/microbiology , Sheep Diseases/parasitology , Sheep Diseases/virology
16.
Benef Microbes ; 11(5): 477-488, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-740509

ABSTRACT

Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.


Subject(s)
Cattle Diseases/therapy , Diarrhea , Lactobacillus johnsonii/metabolism , Lactobacillus reuteri/metabolism , Probiotics/therapeutic use , Animals , Animals, Newborn , Cattle , Cattle Diseases/microbiology , Cattle Diseases/prevention & control , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Cryptosporidiosis/prevention & control , Cytokines/blood , Dairying , Diarrhea/prevention & control , Diarrhea/therapy , Diarrhea/veterinary , Escherichia coli Infections/prevention & control , Escherichia coli Infections/veterinary , Feces/virology , Gastrointestinal Tract/microbiology , Immunoglobulin A/blood , Rotavirus Infections/prevention & control , Rotavirus Infections/veterinary , Salmonella Infections, Animal/prevention & control
17.
Vet Med Sci ; 6(4): 686-694, 2020 11.
Article in English | MEDLINE | ID: covidwho-141637

ABSTRACT

Partial gene sequencing for the bovine coronavirus at the World Genebank is available for many countries, which are distributed unevenly in five continents, but so far, no sequencing of strains has been recorded in Iran. One hundred ninety-four stool samples from calves with diarrhoea less than one-month old were collected from five different geographical regions of country in order to detect coronavirus and characterize it if coronavirus was found. Samples were screened for the presence of BCoV by using a commercially available ELISA kit. Furthermore, RT-PCR was carried out on positive samples for confirmation of the presence of N and S specific genes. Sequencing and phylogenetic analysis was carried out following RT-PCR tests. 7.2% of samples, were positive for BCoV and all stool samples from the South-West, Northeast and West regions of Iran were negative. The results showed that all the strains of coronavirus identified in Iran were completely in independent clusters and that they did not stand in the same cluster as any of the strains identified in other parts of the world. The strains from Iran were quite different from strains in other parts of the world but from the point of similarity these viruses showed some similarities to the European strains, such as those found in France, Croatia, Denmark and Sweden.


Subject(s)
Animals, Newborn , Cattle Diseases/virology , Coronavirus Infections/veterinary , Coronavirus, Bovine , Diarrhea/veterinary , Animals , Cattle , Cattle Diseases/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Diarrhea/epidemiology , Diarrhea/virology , Iran/epidemiology
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