Host Immunocompetence Research Articles

Bone mineral density affects tumor growth by shaping microenvironmental heterogeneity.

Breast cancer bone metastasis is the leading cause of mortality in patients with advanced breast cancer. Although decreased mineral density is a known risk factor for bone metastasis, the underlying mechanisms remain poorly understood because studying the isolated effect of bone mineral density on tumor heterogeneity is challenging with conventional approaches. Here, we investigate how bone mineral content affects tumor growth and microenvironmental complexity in vivo by combining single-cell RNA-sequencing with mineral-containing or mineral-free decellularized bone matrices. We discover that the absence of bone mineral significantly influences fibroblast and immune cell heterogeneity, promoting phenotypes that increase tumor growth and alter the response to injury or disease. Importantly, we observe that the stromal response to matrix mineral content depends on host immunocompetence and the murine tumor model used. Collectively, our findings suggest that bone mineral density affects tumor growth by altering microenvironmental complexity in an organism-dependent manner.

Exploring the relationship between anellovirus load and clinical variables in hospitalized COVID-19 patients: Implications for immune activation and inflammation

ObjectivesAnelloviruses have been linked with host-immunocompetence and inflammation. Here, we studied the anellovirus load in hospitalized COVID-19 patients. MethodsWe collected samples of patients recruited in the DAWN-Plasma trial that received convalescent plasma (CP) therapy (four plasma units) combined with standard of care (SOC) or SOC of alone. Plasma samples were collected on day 0 and 6 of hospitalization and we quantified anellovirus load. With multivariate models, clinical variables were associated with changes in anellovirus load. ResultsSamples were collected on day 0 and 6 of 150 patients (103 CP + SOC and 47 SOC). Anellovirus load was higher on day 0 compared to day 6 and we found a significant drop in SOC patients. Patients receiving immunosuppressive drug had a lower anellovirus load (coefficient: 1.021, 95% confidence interval [CI] 0.270-1.772, P = 0.008), while patients admitted to the emergency room displayed a higher abundance on day 0 (1.308, 95% CI 0.443-2.173, P = 0.003). Unspecific markers of inflammation and organ damage, D-dimer (0.001, 95% CI <0.001-0.001, P = 0.001) and lactate dehydrogenase (0.002, 95% CI 0.001-0.004, P = 0.044), were positively associated with anellovirus load. Finally, anellovirus load on day 0 (–39.9, 95% CI –75.72 to –4.27, P = 0.029) was negatively associated with SARS-CoV-2 antibody response on day. ConclusionThe results showed associations between clinical variables and anellovirus load in COVID-19 patients. Many variables share properties related to host immunocompetence or inflammation. Therefore, we expect that anellovirus abundance displays the net state of immune activation.

Assessing Surveillance of Wildlife Diseases by Determining Mammal Species Vulnerability to Climate Change

Climate change is one of the drivers of wildlife-borne disease emergence, as it can affect species abundance and fitness, host immunocompetence, and interactions with pathogens. To detect emerging wildlife-borne diseases, countries may implement general wildlife-disease surveillance systems. Such surveillance exists in the Netherlands. However, it is unclear how well it covers host species vulnerable to climate change and consequently disease emergence in these species. Therefore, we performed a trait-based vulnerability assessment (TVA) to quantify species vulnerability to climate change for 59 Dutch terrestrial mammals. Species’ vulnerability was estimated based on the magnitude of climatic change within the species’ distribution (exposure), the species’ potential to persist in situ (sensitivity), and the species’ ability to adjust (adaptive capacity). Using these vulnerability categories, we identified priority species at risk for disease emergence due to climate change. Subsequently, we assessed the frequency of occurrence of these priority species compared to other mammal species examined in general wildlife disease surveillance during 2008–2022. We identified 25% of the mammal species to be highly exposed, 24% to be highly sensitive, and 22% to have a low adaptive capacity. The whiskered myotis and the garden dormouse were highly vulnerable (i.e., highly exposed, highly sensitive, and low adaptive capacity), but they are rare in the Netherlands. The Western barbastelle, the pond bat, and the Daubenton’s myotis were potential adapters (highly exposed, highly sensitive, and high adaptive capacity). Species vulnerable to climate change were relatively poorly represented in current general surveillance. Our research shows a comprehensive approach that considers both exposures to climate change and ecological factors to assess vulnerability. TVAs, as presented in this study, can easily be adapted to include extra drivers and species, and we would therefore recommend surveillance institutes to consider integrating these types of assessments for evaluating and improving surveillance for wildlife-borne disease emergence.

Remotely sensed localised primary production anomalies predict the burden and community structure of infection in long-term rodent datasets.

The increasing frequency and cost of zoonotic disease emergence due to global change have led to calls for the primary surveillance of wildlife. This should be facilitated by the ready availability of remotely sensed environmental data, given the importance of the environment in determining infectious disease dynamics. However, there has been little evaluation of the temporal predictiveness of remotely sensed environmental data for infection reservoirs in vertebrate hosts due to a deficit of corresponding high-quality long-term infection datasets. Here we employ two unique decade-spanning datasets for assemblages of infectious agents, including zoonotic agents, in rodents in stable habitats. Such stable habitats are important, as they provide the baseline sets of pathogens for the interactions within degrading habitats that have been identified as hotspots for zoonotic emergence. We focus on the enhanced vegetation index (EVI), a measure of vegetation greening that equates to primary productivity, reasoning that this would modulate infectious agent populations via trophic cascades determining host population density or immunocompetence. We found that EVI, in analyses with data standardised by site, inversely predicted more than one-third of the variation in an index of infectious agent total abundance. Moreover, in bipartite host occupancy networks, weighted network statistics (connectance and modularity) were linked to total abundance and were also predicted by EVI. Infectious agent abundance and, perhaps, community structure are likely to influence infection risk and, in turn, the probability of transboundary emergence. Thus, the present results, which were consistent in disparate forest and desert systems, provide proof-of-principle that within-site fluctuations in satellite-derived greenness indices can furnish useful forecasting that could focus primary surveillance. In relation to the well-documented global greening trend of recent decades, the present results predict declining infection burden in wild vertebrates in stable habitats; but if greening trends were to be reversed, this might magnify the already upwards trend in zoonotic emergence.

Pyogenic sacroiliitis caused by Salmonella schwarzengrund in a young healthy woman: a case report and literature review

BackgroundSalmonella species are a leading cause of diarrheal diseases worldwide. Recent epidemiological studies have shown that Salmonella schwarzengrund (S. schwarzengrund) is highly prevalent in various regions. Herein, we report that S. schwarzengrund caused sacroiliac joint (SIJ) infection with septic shock in a young woman, although she was immunocompetent.Case presentationA 20-year-old woman presented with left hip pain, accompanied by vasopressor-requiring hypotension. Her imaging examinations showed fluid collection in her SIJ and a small abscess in the left iliac muscle. Later, the blood and aspiration fluid culture and genetic analysis revealed the presence of S. schwarzengrund. We diagnosed sacroiliac joint (SIJ) infection with septic shock caused by S. schwarzengrund. Her condition improved after performing several interventional radiology (IVR) procedures for SIJ abscesses and providing appropriate antibiotic treatment. Finally, she was discharged without any sequelae. Screening tests and genetic analysis about her immunodeficiency did not indicate a congenital disorder.ConclusionThese clinical courses indicate that S. schwarzengrund could cause the fatal SIJ infection irrespective of the host immunocompetence. Considering the recent increase in the diagnostic rate of S. schwarzengrund, this case emphasized the need to be more cautious about Salmonella species infection.

Disease state associated with chronic toe lesions in hellbenders may alter anti-chytrid skin defenses

Hellbenders (Cryptobranchus alleganiensis) are large, aquatic salamanders from the eastern United States. Both subspecies, eastern and Ozark hellbenders, have experienced declines resulting in federal listing of Ozark hellbenders. The globally distributed chytrid fungus, Batrachochytrium dendrobatidis (Bd) has been detected in both subspecies, and Batrachochytrium salamandrivorans (Bsal) poses a new threat if introduced into North America. Ozark hellbenders also suffer a high prevalence of toe lesions of unknown etiology, with changes in host immunocompetence hypothesized to contribute. Antimicrobial peptides (AMPs) secreted from dermal granular glands may play a role in hellbender health. We collected skin secretions from free-ranging hellbenders and enriched them for small cationic peptides used for growth inhibition assays against Bd and Bsal. Generalized linear mixed models revealed the presence of active toe lesions as the strongest and only significant predictor of decreased Bd inhibition by skin peptides. We also found skin secretions were more inhibitory of Bsal than Bd. MALDI-TOF mass spectrometry revealed candidate peptides responsible for anti-chytrid activity. Results support the hypothesis that hellbender skin secretions are important for innate immunity against chytrid pathogens, and decreased production or release of skin peptides may be linked to other sub-lethal effects of disease associated with toe lesions.

On maternity and the stronger immune response in women

Medical research reports that women often exhibit stronger immune responses than men, while pathogens tend to be more virulent in men. Current explanations cannot account for this pattern, creating an obstacle for our understanding of infectious-disease outcomes and the incidence of autoimmune diseases. We offer an alternative explanation that relies on a fundamental difference between the sexes: maternity and the opportunities it creates for transmission of pathogens from mother to child (vertical transmission). Our explanation relies on a mathematical model of the co-evolution of host immunocompetence and pathogen virulence. Here, we show that when there is sufficient vertical transmission co-evolution leads women to defend strongly against temperate pathogens and men to defend weakly against aggressive pathogens, in keeping with medical observations. From a more applied perspective, we argue that limiting vertical transmission of infections would alleviate the disproportionate incidence of autoimmune diseases in women over evolutionary time.

Immunomodulatory effect and histological alteration of thermally oxidized sunflower oil in male Wistar rats

Many foods are prepared by deep-frying as this provides unique flavors/textures that improve overall palatability to consumers. Sunflower oil is one of the most widely-used frying oils in the world. However, during frying, fats in the foodstuff are heated to &gt; 150° C and concurrently come into contact with agents found in the air, water, and other foods being cooked at the same time. Since long-term consumption of oxidized/oxidation products can contribute to the development of a variety of pathologies. Used cooking oil has become of increased concern to both health administrators and consumers. Few studies have sought to examine potential immunomodulatory effects from exposures to sunflower oil or its oxidized/oxidation products. To address this gap in knowledge, here, sunflower oil was used to fry potatoes at 190° C, every 30 min; a new 100 g batch of slices was cooked. Frying was performed continuously for 5h/day for 2 and 4 days (10 and 20 h total), and then the parental uncooked oil and each of the used oils were provided to Wistar rats in their diet (at 20% level) for a total of 10 weeks. Measures of body weight\food intake indicated that diets containing the used oils led to slightly reduced food intakes and host weights. Kidney weights were not affected by consumption of the two used oils, but the liver was enlarged in rats fed with the oil treated for 20 h. Evaluation of key lipid-serum parameters, i.e., total cholesterol, HDL cholesterol, and triglycerides, revealed a diet-related decrease in each; oxidized fats reduce their concentration compared to fresh fats. Conversely, serum LDL cholesterol levels were increased. Histological analyses indicated that consumption of the oxidized oils caused both kidney (e.g., tubular/glomerular dilation, vascular congestion, inflammation, tubular necrosis) and liver (e.g., vascular congestion, inflammation, necrosis) damages. Assessments of host immune function, i.e., ability to form antibody to ovalbumin (OVA) challenge, indicated that in rats fed the used oil, there were significant decreases in serum anti-OVA antibody levels. This suggested that host immunocompetence could be compromised as a result of long-term consumption of a diet containing a relatively high (i.e., 20%) content of used sunflower oils.

In an arms race between host and parasite, a lungworm's ability to infect a toad is determined by host susceptibility not parasite preference.

Evolutionary arms races can alter both parasite infectivity and host resistance, and it is difficult to separate the effects of these twin determinants of infection outcomes. We used a co-introduced, invasive host-parasite system (the lungworm Rhabdias pseudosphaerocephala and cane toads Rhinella marina), where rapid adaptation and dispersal have led to population differences in infection resistance. We quantified behavioural responses of parasite larvae to skin-chemical cues of toads from different invasive populations, and rates at which juvenile hosts became infected following standardized exposure to lungworms. Chemical cues from toad skin altered host-seeking behaviour by parasites, similarly among populations. The number of infection attempts (parasite larvae entering the host's body) also did not differ between populations, but rates of successful infection (establishment of adult worm in host lungs) were higher for range-edge toads than for range-core conspecifics. Thus, lower resistance to parasite infection in range-edge juvenile toads appears to be due to less effective immune defences of the host rather than differential behavioural responses of the parasite. In this ongoing host-parasite arms race, changing outcomes appear to be driven by shifts in host immunocompetence.

Immunological Determinants of Liver Transplant Outcomes Uncovered by the Rat Model.

For many individuals with end-stage liver disease, the only treatment option is liver transplantation. However, liver transplant rejection is observed in 24%–80% of transplant patients and lifelong drug regimens that follow the transplant procedure lead to serious side effects. Furthermore, the pool of donor livers available for transplantation is far less than the demand. Well-characterized and physiologically relevant models of liver transplantation are crucial to a deeper understanding of the cellular processes governing the outcomes of liver transplantation and serve as a platform for testing new therapeutic strategies to enhance graft acceptance. Such a model has been found in the rat transplant model, which has an advantageous size for surgical procedures, similar postoperative immunological progression, and high genome match to the human liver. From rat liver transplant studies published in the last 5 years, it is clear that the rat model serves as a strong platform to elucidate transplant immunological mechanisms. Using the model, we have begun to uncover potential players and possible therapeutic targets to restore liver tolerance and preserve host immunocompetence. Here, we present an overview of recent literature for rat liver transplant models, with an aim to highlight the value of the models and to provide future perspectives on how these models could be further characterized to enhance the overall value of rat models to the field of liver transplantation.

Stage-Dependent Within-Individual Comparison Reveals SIV-Specific Activation/Exhaustion Shift in Rhesus Macaques.

It is challenging to trace the complicated individual-based variations of HIV-specific immunocompetence shift during the successful antiretroviral therapy (ART) era. Using eight rhesus monkeys simulating a longitudinal stage-dependent cohort (baseline-SIV acute infection-SIV suppression by ART-ART withdrawal), baseline immunocompetence monitoring for 28 days (SIV-negative stage, SN) was compared with host immunocompetence undergoing 90-day ART treatment (SIV-suppressed stage, SS) to reveal the SIV-specific immunity shift aroused by undetectable individual viral replication. During acute SIV infection for 98 days (SIV-emerged stage, SE), immune activation was compared with re-immune activation post ART for 49-day follow-up (SIV-rebounded stage, SR) to reveal the SIV-specific immune activation variation aroused by detectable individual viral replication. Individual immunocompetence was measured by co-expression of CD4, CD8, CD38, HLA-DR, CCR7, CD45RA, and PD-1 on T cells and a cytokine panel. Compared with SN, mild immune activation/exhaustion was characterized by increased CD38+ HLA-DR– CD4+/CD8+ T-cell subsets and PD-1+ memory CD4+/CD8+ T-cell subsets with three elevated cytokines (MIP-1β, IL-8, and IL-10) significantly emerged in SS. Compared with SE, SR produced more exhaustion characterized by increased PD-1+ CD4+ TCM cells and decreased PD-1+ CD4+ TEM cells with four elevated pro-inflammatory cytokines (IFN-γ, IL-1β, IL-6, and TNF-α). By such individualized stage-dependent comparison, the sustainable immune activation was found from activation/exhaustion shifted into exhaustion during the longitudinal viral persistence. Further, validated SIV accelerates host immunosenescence continuously independent of viral replication.

S2400 Typhoid Fever: An Unusual Cause of Acute Hepatitis

INTRODUCTION: Typhoid fever, a disease highest in incidence in South Asia, is due to Salmonellae ingestion via feces-contaminated food or water. While hepatic involvement is not rare given colonization of reticuloendothelial tissues, an acute hepatitis picture, as seen here, is unusual. CASE DESCRIPTION/METHODS: A 25 year old female without past medical history presented febrile, tachycardic, and hypotensive after 8 days of fatigue, fevers, chills, myalgias, headaches, nausea, and emesis following a trip to Miami. She had taken daily Acetaminophen since onset and denied other medication, herbal, and alcohol consumption. Of note, the patient emigrated to the United States 9 months prior and made a 3 month trip home to the Indian subcontinent 3 weeks before presentation. While there, she took Acetaminophen and a course of Amoxicillin. She and multiple family members also experienced fever, nausea, emesis, and diarrhea after consuming raw vegetables. Notable labs include leukopenia at 4.1, AST 593, ALT 560, and ALP 148. Urgent care labs 2 days prior were significant for AST 68, ALT 59, ALP 106, and negative hepatitis serologies. She received Ceftriaxone, IV fluids, and NAC, though plasma Acetaminophen level resulted as < 5 mcg. After blood cultures yielded gram negative rod bacteremia, antibiotics were changed to Piperacillin/Tazobactam. Abdominal ultrasound was unremarkable and triple phase CT showed mild hepatic heterogeneity. Repeat hepatitis serologies, CMV, EBV, autoimmune markers, malarial smears, and HIV were among tests ordered to determine acute transaminitis etiology. Blood cultures eventually revealed Salmonella enterica susceptible to Amoxicillin. Transaminases continued to downtrend after 5 days of hospitalization and she was successfully discharged home. DISCUSSION: Acute febrile illness in a patient recently abroad prompts investigation into diseases endemic to the region from which a patient has travelled. For the Indian subcontinent, typhoid fever may be a culprit, but its nonspecific presentation renders suspicion difficult especially when complicated by acute transaminitis and DILI concerns. As with our patient, diseases such as malaria, hepatitis, and HIV should also be considered. Depending on individual inoculum as well as host immunocompetence, incubation may be 5-21 days with prolonged fever for up to 1 month if the disease goes untreated. Interestingly, leukopenia is noted in 15-25% of cases. Blood cultures, integral to the work-up of recurrent fever, ultimately led to our diagnosis.

The novel insecticides flupyradifurone and sulfoxaflor do not act synergistically with viral pathogens in reducing honey bee (Apis mellifera) survival but sulfoxaflor modulates host immunocompetence.

The decline of insect pollinators threatens global food security. A major potential cause of decline is considered to be the interaction between environmental stressors, particularly between exposure to pesticides and pathogens. To explore pesticide-pathogen interactions in an important pollinator insect, the honey bee, we used two new nicotinic acetylcholine receptor agonist insecticides (nACHRs), flupyradifurone (FPF) and sulfoxaflor (SULF), at sublethal and field-realistic doses in a fully crossed experimental design with three common viral honey bee pathogens, Black queen cell virus (BQCV) and Deformed wing virus (DWV) genotypes A and B. Through laboratory experiments in which treatments were administered singly or in combination to individual insects, we recorded harmful effects of FPF and pathogens on honey bee survival and immune gene expression. Though we found no evidence of synergistic interactions among stressors on either honey bee survival or viral load, the combined treatment SULF and DWV-B led to a synergistic upregulation of dicer-like gene expression. We conclude that common viral pathogens pose a major threat to honey bees, while co-exposure to these novel nACHR insecticides does not significantly exacerbate viral impacts on host survival in the laboratory.

Pathologic findings and causes of death in bottlenose dolphins Tursiops truncatus stranded along the Georgia coast, USA (2007-2013).

Between 2007 and 2013, before the 2013 cetacean morbillivirus outbreak, 26 fresh bottlenose dolphin carcasses were necropsied on the coast of Georgia, USA. Here, we present the pathological and microbiological findings associated with their most likely causes of death. The primary cause of death was determined in 25 individuals and included systemic bacterial infection (n = 7), verminous and bacterial bronchopneumonia (n = 5), drowning/entanglement (n = 5), disseminated histoplasmosis (n = 1), intestinal intussusception (n = 1), vegetative endocarditis (n = 1), meningitis (n = 1), necrotizing dermatitis (n = 1), disseminated angiomatosis (n = 1), emaciation (n = 1) and stingray spine trauma (n = 1). Histiocytic and eosinophilic bronchopneumonia associated with Halocerchus sp. infection was observed in 69% of the animals (18/26) and eosinophilic gastritis due to Anisakidae nematodes was found in 36% of the examined stomachs (8/22). Moderate to severe eosinophilic pancreatitis with fibrosis was observed in 4 animals infected with Brachycladiidae trematodes. Proliferative and ulcerative lymphoplasmacytic dermatitis was found in 5 animals and was considered to contribute to deteriorated health status in 2 calves. Pulmonary and lymph node angiomatosis were observed in 15 and 10 animals, respectively. In at least 2 animals, the concentration of polychlorinated biphenyls (PCBs) in the blubber exceeded 1500 µg g-1 of lipid. Bottlenose dolphins stranded on the Georgia coast have a wide range of inflammatory lesions associated with a variety of helminth, bacterial, and fungal pathogens. Some resident animals have also been exposed to high levels of PCB contamination, which could reduce host immunocompetence. Higher exposure to these or other pathogens could result in further decline in the health of resident and migrant dolphin populations in this region.

Extended-Spectrum-β-Lactamase- and Plasmid AmpC-Producing Escherichia coli Causing Community-Onset Bloodstream Infection: Association of Bacterial Clones and Virulence Genes with Septic Shock, Source of Infection, and Recurrence

Invasive infections due to extended-spectrum-β-lactamase- and pAmpC-producing Escherichia coli (ESBL/pAmpC-EC) are an important cause of morbidity, often caused by the high-risk clone sequence type (ST131) and isolates classified as extraintestinal pathogenic E. coli (ExPEC). The relative influence of host immunocompetence versus microbiological virulence factors in the acquisition and outcome of bloodstream infections (BSI) is poorly understood. Herein, we used whole-genome sequencing on 278 blood culture isolates of ESBL/pAmpC-EC from 260 patients with community-onset BSI collected from 2012 to 2015 in Stockholm to study the association of virulence genes, sequence types, and antimicrobial resistance with severity of disease, infection source, ESBL/pAmpC-EC BSI low-risk patients, and patients with repeated episodes. ST131 subclade C2 comprised 29% of all patients. Factors associated with septic shock in multivariable analysis were patient host factors (hematologic cancer or transplantation and reduced daily living activity), presence of the E. coli virulence factor iss (increased serum survival), absence of phenotypic multidrug resistance, and absence of the genes pap and hsp Adhesins, particularly pap, were associated with urinary tract infection (UTI) source, while isolates from post-prostate biopsy sepsis had a low overall number of virulence operons, including adhesins, and commonly belonged to ST131 clades A, B, and subclade C1, ST1193, and ST648. ST131 was associated with recurrent episodes. In conclusion, the most interesting finding is the association of iss with septic shock. Adhesins are important for UTI pathogenesis, while otherwise low-pathogenic isolates from the microbiota can cause post-prostate biopsy sepsis.

Efectos del cambio climático sobre las interacciones ave-parásito

Garcia del Rio, M., Castano-Vazquez, F., Merino, S. 2020. Effects of climate change on bird-parasite interactions. Ecosistemas 29(2):1981. https://doi.org/10.7818/ECOS.1981 During the last years, models on the effects of climate change predict the arrival of milder climates to higher latitudes and altitudes, and as a consequence, the spread of disease from lower latitudes and altitudes. Bird-parasite interactions are not an exception and could be affected by these changes. However, several reviews on the effects of climate change on birds and parasites conclude that effects of climate on these interactions could be diverse and complex and, in general, difficult to predict. In this article we review some studies reporting climatic effects on bird-parasite relationships, showing different aspects that may interact in these cases. Biodiversity, density of organisms, both of hosts or parasites, virulence of parasites and host immunocompetence, are key factors to understand the effects of climate change on bird-parasite interactions. More empirical work is clearly needed to show the level of impact of climate change on birds and parasite populations as well as on their capacity of adaptation to those changes.

Production of Germ-Free Fast-Growing Broilers from a Commercial Line for Microbiota Studies.

Studies of the gut microbiota contribution to the host physiology and immunocompetence are facilitated by the availability of germ-free animal models, which are considered the gold standard. Nesting birds are ideal models for the production of germ-free animals since there is no need to raise their relatives under sterile conditions. Germ-free chickens are mainly generated from specific-pathogen-free (SPF) experimental lines, which are poorly representative of commercial chicken lines.The method proposed here allowed the production of germ-free chickens from the fast growing broiler line Ross PM3, commonly used by the poultry industry.Eggs were quickly collected after laying at a broiler breeder farm.They underwent a strict decontamination process from the collection to the introduction in a sterile egg hatching isolator.The chicks have been hatched and kept in these sterile isolators during the period necessary to control their sterility. Originally developed for an experimental SPF white leghorn line, the present protocol has been adapted not only to the Ross PM3 broiler line but also to quails. It therefore represents a robust and readily adaptable procedure to other poultry species and nesting birds of economic, biological or ecological relevance.

SARS-CoV-2: Micronutrient Optimization in Supporting Host Immunocompetence

SARS-CoV-2: Micronutrient Optimization in Supporting Host Immunocompetence

Env diversity-dependent protection of the attenuated equine infectious anaemia virus vaccine

ABSTRACT Lentiviruses harbour high genetic variability for efficient evasion from host immunity. An attenuated equine infectious anaemia (EIA) vaccine was developed decades ago in China and presented remarkably robust protection against EIA. The vaccine was recently proven to have high genomic diversity, particular in env. However, how and to what extent the high env diversity relates to immune protection remains unclear. In this study, we compared immune protections and responses of three groups of horses stimulated by the high-diversity vaccine EIAV_HD, a single molecular clone of the vaccine EIAV_LD with low env diversity, as well as a constructed vaccine strain EIAV_MD with moderate env diversity. The disparity of virus-host interactions between three env diversity-varied groups (5 horses in each group) was evaluated using clinical manifestation, pathological scores, and env-specific antibody. We found the highest titres of env antibodies (Abs) or neutralizing Abs (nAbs) in the EIAV_HD group, followed by the EIAV_MD group, and the lowest titres in the EIAV_LD group (P<0.05). The occurrence of disease/death was different between EIAV_HD group (1/0), EIAV_MD (2/2), and EIAV_LD group (4/2). A similar env diversity-related linear relationship was observed in the clinical manifestations and pathological changes. This diversity-dependent disparity in changes between the three groups was more distinct after immunosuppression, suggesting that env diversity plays an important role in protection under low host immunocompetence. In summary, inoculation with vaccines with higher genetic diversity could present broader and more efficient protection. Our findings strongly suggest that an abundance of Env antigens are required for efficient protection against lentiviruses.

A new approach to the management of emerging diseases of aquatic animals.

Since 1970, aquaculture has grown at a rate of between 5% and 10% per annum. It has achieved this by expanding into new areas, farming new (often non-native) species and intensifying production. These features of aquaculture, combined with large-scale movements of animals, have driven disease emergence, with negative consequences for both production and biodiversity. Efforts to improve the management of emerging diseases of aquatic animals must include actions to reduce the rate of disease emergence, enhance disease detection and reporting, and improve responses to prevent disease spread. The rate of disease emergence can be reduced by understanding the underpinning mechanisms and developing measures to mitigate them. The three principal mechanisms of disease emergence, namely, host switching, decreased host immunocompetence and increased pathogen virulence, have many drivers. The most important of these drivers are those that expose susceptible hosts to novel pathogens (e.g. the introduction of non-native hosts, translocation of pathogens, and increased interaction between wild and farmed populations), followed by host switching. Exposure to wild populations can be reduced through infrastructure and management measures to reduce escapes or exclude wild animals (e.g. barrier nets, filtration and closed-confinement technology). A high standard of health management ensures immunocompetence and resistance to putative new pathogens and strains, and thus reduces the rate of emergence. Appropriate site selection and husbandry can reduce the likelihood of pathogens developing increased virulence by preventing their continuous cycling in geographically or temporally linked populations. The under-reporting of emerging aquatic animal diseases constrains appropriate investigation and timely response. At the producer level, employing information and communications technology (e.g. smartphone applications and Cloud computing) to collect and manage data, coupled with a farmer-centric approach to surveillance, could improve reporting. In addition, reporting behaviours must be understood and disincentives mitigated. At the international level, improving the reporting of emerging diseases to the World Organisation for Animal Health allows Member Countries to implement appropriate measures to reduce transboundary spread. Reporting would be incentivised if the global response included the provision of support to low-income countries to, in the short term, control a reported emerging disease, and, in the longer term, develop aquatic animal health services. Early detection and reporting of emerging diseases are only of benefit if Competent Authorities' responses prevent disease spread. Effective responses to emerging diseases are challenging because basic information and tools are often lacking. Consequently, responses are likely to be sub-optimal unless contingency plans have been developed and tested, and decision-making arrangements have been well established.