Use of convalescent plasma to treat COVID-19: case studies.

There have been several efforts to minimize the effects caused by the COVID-19 virus around the world. Vaccines were developed in record time and alternative therapies were studied and applied in several countries, such as the use of plasma from recovered patients. Identifying, systematically evaluating and summarizing the best available scientific evidence on the efficacy and safety of using plasma from recovered COVID-19 patients remains the objective of this study. The studies carried out showed that the application of convalescent plasma contributes to the reduction of mortality, viral load and length of hospital stay. However, the effectiveness of the therapy still raises doubts due to the number of patients evaluated in clinical studies, in addition to its high cost and limitations in terms of availability and implementation, with the drug being authorized only for hospital use.

Value profile for respiratory syncytial virus vaccines and monoclonal antibodies.

Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Allele mining in gene encoding fc fragment of IgG receptor, transporter, alpha (FCGRT) and association of nucleotide variants with passive transfer of immunity in neonatal buffalo calves.

BACKGROUND: Neonatal Fc receptors (FcRn) mediate the transcytosis of IgG present in colostrum across absorptive gut epithelium of newborn calves. FcRn receptor is a heterodimer composed of two polypeptides encoded by FCGRT (Fc fragment of IgG Receptor Transporter neonatal) and B2M (Beta 2 microglobulin) genes. Polymorphism in FCGRT gene may have a bearing on absorption of colostral immunoglobulins by neonatal buffalo calves, thereby affecting their immune status and susceptibility to diseases. The primary aim of our study was to mine alleles and single nucleotide polymorphs in the FCGRT gene and determine their association with the levels of IgG in serum of neonatal buffalo calves. METHODS AND RESULTS: On the basis of serum IgG levels estimated by indirect ELISA in 80 newborn calves, 20 calves each with highest and lowest IgG concentration were selected to study polymorphism in the FCGRT gene. The exonic regions of this gene were amplified in nine fragments which were subjected to PCR-SSCP to detect variations followed by the sequencing of variants to locate the SNPs. A total of nine SNPs (7 in introns and 2 in exons) were detected in four polymorphic fragments. Association study based on Odds ratios (ORs) with 95% Confidence Interval (CIs) established that the SNP G40T in fragment 3 has a significant (P < 0.05) bearing on IgG level in serum of neonatal buffalo calves. CONCLUSION: Genetic variation in FCGRT gene in buffalo calves was found to be associated with their serum IgG levels in neonatal stage which may have implications in calf survival and growth vis-à-vis inadequate transfer of passive immunity.

Effect of Supplementation with Saccharomyces cerevisiae and ß-glucans to Mares During Late Gestation on Colostrum Quality and Passive Transfer of Immunity in Foals.

The objective of this study was to determine whether supplementation with Saccharomyces cerevisiae or ß-glucan, in the maternal diet during late pregnancy affects the concentration of total IgG in the colostrum of mares and influences the concentration of IgG in its foals. A total of 21 pregnant mares were used, aged 6±2 years, 3±1 pregnancies, 450±50kg in weight, and they were distributed into three groups: the control group (n=7); the S. cerevisiae group (n=7), which received 1010CFU of S. cerevisiae orally; and the ß-glucan group (n=7), which received 0.35g of ß-glucan orally. All groups started from the 300th day of their pregnancies until delivery. Samples of colostrum and serum from the mares were collected immediately after delivery. Blood samples from their foals were collected 12h after birth. The IgG measurement was performed using radial immunodiffusion. The results underwent a variance analysis. Higher concentrations of IgG were observed in the colostrum of mares that were supplemented with ß-glucans (74.14±15.25 g/L) when compared to the control group (53.80g±10.95g/L). Serum IgG concentrations of foals born to mares supplemented with Saccharomyces cerevisiae (11.57±5.05 g/L) showed a significant difference, with a higher concentration of IgG in the serum compared to the control group. Therefore, this study provides evidence that manipulation of the mares' diets in late gestation to add ß-glucan increased the IgG concentration in their colostrum. The addition of S. cerevisiae appears to improve the concentration of IgG in their foals within 12h after birth.

In search for a panacea for coronavirus disease-19: Analysis of ongoing clinical trials for the management of coronavirus disease-19 pandemic in India.

OBJECTIVE: To analyze the clinical trials that are registered on the Clinical Trial Registry of India (CTRI) portal for a year, for the treatment, prevention, and supportive therapy of coronavirus disease-19 (COVID-19). MATERIALS AND METHODS: All the trials registered on CTRI (since January 2020 till January 2021) for therapeutic, preventive, and supportive interventions for COVID-19 were searched with the keywords "Coronavirus," "COVID-19," "SARS-COV-2," and "2019-nCoV". These registered studies were analyzed as follows: Trials under different systems of Medicine-Allopathy/Homeopathy/Ayurveda/Unani/Yoga/Naturopathy. The Allopathy trials were further analyzed in detail: Intervention, design, comparator, number of subjects, duration, and approvals taken. RESULTS: A total of 1597 records were found. After excluding the overlaps, behavioral and other studies conducted to understand the diagnosis, epidemiology, a total of 419 registered studies were included for further analysis. Out of these 419 studies, 166 (39.6%) were in Ayurveda, 154 (36.7%) in Allopathy, 33 (7.8%) in Homeopathy, 30 (7%) in Unani/Siddha, 18 (4.3%) in Yoga and Naturopathy and 18 (4.3%) in Nutraceuticals. A total of 264 interventions had been registered in 419 clinical trials. Sixty-seven interventions were being studied under allopathy in 154 studies. Same product was being evaluated in differently designed protocols with different endpoints. Maximum number of trials and subjects were for Hydroxychloroquine 25 (17,998), Ivermectin 11 (2820), Convalescent Plasma 11 (3982), Remdesivir 8 (3725), Tocilizumab 6 (884), and Azithromycin 6 (582). CONCLUSIONS: In response to the COVID-19 pandemic, Indian researchers came forward from all the systems of medicine to evaluate interventions for prophylaxis or treatment of the disease. The involvement of AYUSH systems of medicine was specifically more in this regard. A wide variation and heterogeneity in doses and outcomes were observed in trial designs which might make it difficult to generalize the study results when they are made available. Urgent analyses of studies involving interventions on the treatment advisory of the Government may help the healthcare providers take more informed decisions for managing COVID-19 patients in India.

Comparative efficacy and safety of pharmacological interventions for severe COVID-19 patients: An updated network meta-analysis of 48 randomized controlled trials.

BACKGROUND: To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19. METHODS: We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs). RESULTS: We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients. CONCLUSION: This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.

Colostrum management practices that improve the transfer of passive immunity in neonatal dairy calves: A scoping review.

The objective of this scoping review was to describe the literature on the characteristics and management practices of colostrum feeding and their associations with the level of transfer of passive immunity (TPI) in dairy calves. Observational and experimental studies were searched in 5 electronic databases and 3 conference proceedings. Two reviewers independently screened primary studies, either analytic observational or experimental studies written in English. Studies on dairy or dual-purpose calves with passive immunity analyzed by blood sampling between 1 to 9 days of age were included. All studies had to compare at least one colostrum intervention or risk factor and their association with passive immunity. Of the 3,675 initially identified studies, 256 were included in this synthesis. One hundred and ninety-five were controlled trials, 57 were cohort studies, and 4 were cross-sectional studies. The effect of colostral quantity at first feeding was investigated in 30 controlled studies including studies that were comparable to each other. The effect of colostral quality was explored in 24 controlled studies with inconsistent criteria used to define the quality. The effect of the timing of first feeding of colostrum was investigated in 21 controlled studies, where the timing of feeding ranged widely from immediately after birth to 60 h of age. Only 4 controlled studies evaluated the relationship between bacterial load in the colostrum and TPI in dairy calves. Of the 256 total studies, 222 assessed blood IgG concentration while 107 measured blood total protein concentration. We identified a gap in knowledge on the association between passive immunity in dairy calves and the bacterial load in colostrum, or the timing of harvesting colostrum from the dam. A possible quantitative synthesis could be conducted among the studies that evaluated colostral quantity at the first feeding in relation to TPI in dairy calves.

[Management of immunocompromised renal transplant patients infected with coronavirus disease 2019].

OBJECTIVE: To analyze the treatment process of a renal transplant patient infected with coronavirus disease 2019 (COVID-19), and discuss the management strategy for the immunocompromised hosts. METHODS: The diagnosis and treatment of a case of transplant patients with COVID-19 admitted to Horgos designated hospital of Xinjiang Uygur Autonomous Region in October 2021 were reviewed. The medical history and laboratory and imaging examination treatment and outcome of this case were analyzed. RESULTS: The recipient was a middle-aged male with a time from renal transplantation of 3 years. The onset was moderate to low fever, accompanied by cough and fatigue. Chest CT showed multiple ground glass shadows under the pleura of both lungs, mainly in both lower lungs, gradually worsening until "white lung" appeared, with early renal and cardiac insufficiency. In the course of treatment, immunosuppressants were reduced and the dosage of glucocorticoid was increased. In the early stage, due to renal insufficiency and hyperkalemia, dialysis was conducted for 3 times. Oral abidol and Lianhua Qingwen capsule were given as antiviral and anti-infection treatment. Special immunoglobulin and convalescent plasma of COVID-19 were used to boost the immunity of patients. The patient was eventually clinically cured. CONCLUSIONS: The clinical manifestations and diagnosis of COVID-19 for the kidney transplantation recipient are not significantly different from other populations, but immunocompromised hosts are more likely to suffer from organ dysfunction. The adjustment of immunosuppressants and glucocorticoids, respiratory support, selection of antibiotics, organ protection, nutritional support and traditional Chinese medicine intervention in the treatment of renal transplant recipients with severe COVID-19 need further discussion.

The transfer of passive immunity in calves born at pasture.

Calf and dam separation is an area of growing public interest, and timely separation is also a practical challenge for pastoral farmers to achieve for all calves. Very few studies have investigated the success of leaving calves with their dams in pastoral conditions, so this observational study assessed serum total protein (STP) in calves born at pasture and left to suckle from their dams for up to 24 h. It also investigated failure of transfer of passive immunity (FPT) once calves had been provided colostrum from the farmer and some factors that may contribute to the risk of FPT. Over 2 years, 8 farms (4 in the North Island, 4 in South Island of New Zealand) were involved in an observational study where cows and calves were observed for 24 h a day for 2 wk per farm. Observers recorded the time from birth to first suckling, number of suckling events, time of calf removal from the dam, and ambient temperature. Calves were blood sampled on arrival at housing, before receiving colostrum from the farmer (d 1), and again 2 d later (d 3) to test for STP concentration. On d 1, 689 calves had blood samples collected, at a median of 11.5 (interquartile range 5.6 to 19.2) hours postbirth. Of these, 283 calves [41.1%; 95% confidence interval (CI) 37.4 to 44.9%] had STP >52 g/L (proportion by farm ranged from 10 to 78%). On d 3, 680 blood samples were collected, of which 16.0% (95% CI 13.5 to 19.0) had FPT (STP ≤52 g/L) with proportion by farm ranging from 2.5 to 31.6%. The FPT risk at d 3 in calves that did not suckle before housing was 2.91 (95% CI 2.04 to 4.13) times the risk in calves that suckled. For every hour longer postbirth that it took for a calf to have its first suckling event, odds of FPT at d 3 increased by 1.21 (95% CI 1.08 to 1.36) times, and compared with calves that only suckled once, calves that suckled 2, 3-5, or >5 times had 0.42 (95% CI 0.15 to 0.99), 0.35 (95% CI 0.15 to 0.76), and 0.10 (95% CI 0.005 to 0.47) times the odds of FPT, respectively. For every 1-percentage-point increase in the Brix % of the colostrum, the odds of FPT decreased by 33% (95% CI 24- to 42). Calves that suckled in the paddock and were fed colostrum with ≥22% Brix had the highest STP, and lowest odds of FPT, of any suckling/Brix % combination. There was a trend for STP to be greater in calves that suckled in the paddock and fed <22% Brix compared with calves that did not suckle in the paddock and fed ≥22% Brix. However, the calves in the former group also tended to have a greater risk of FPT at d 3, and a greater STP variability. There were very large between-farm variabilities for rates of suckling, colostrum feeding, and FPT risk that urgently require further investigation for calves born at pasture.

Prevalence of failure of passive immunity transfer in Australian non-replacement dairy calves.

Failure of passive immunity transfer (FPIT) increases the risk of morbidity and mortality in dairy calves. The prevalence of FPIT in dairy calves has generally been reported to be high, with FPIT estimated to occur in 38%-42% of Australian dairy calves. However, the focus of previous studies has been on replacement heifer calves. Our aim was to assess the prevalence of FPIT in Victorian bobby calves (non-replacement dairy calves). We collected blood samples from 3608 bobby calves at three abattoirs at exsanguination, and measured serum total protein as an indicator of passive transfer. We found that 36% of bobby calves showed evidence of FPIT (serum total protein ≤52 g/L), and 50% of calves had poor or fair passive transfer (<58 g/L). When a subset of calves (from farms with more than five calves in the dataset) was analysed using a linear mixed model, Jersey calves and crossbred/other calves had an estimated 5.3 g/L and 5.1 g/L higher serum total protein concentration, respectively, than Holstein-Friesian calves (P < 0.001). Our results suggest that the prevalence of FPIT in bobby calves at abattoirs is similar to that reported in dairy heifer calves sampled on farms. A high prevalence of FPIT has implications for bobby calf morbidity and mortality, as well as calf viability and profitability for dairy-beef production.

How do I implement an outpatient program for the administration of convalescent plasma for COVID-19?

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.

Potential therapeutic options for COVID-19: an update on current evidence.

SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.

Current Treatments and Therapeutic Options for COVID-19 Patients: A Systematic Review.

INTRODUCTION: COVID-19 is the third rising epidemic in the 21st century that quickly turned into a worldwide pandemic. Many clinical studies have been achieved to investigate treatments to confront COVID-19. Therefore, we conducted a systematic review to describe the recent treatment strategies to treat COVID-19 patients. METHODS: A systematic search was performed in the databases of PubMed, Scopus, Embase, Science direct, Up to date, and Web of Science using the keywords of Coronavirus, COVID-19, SARS-CoV-2, Novel Coronavirus, 2019-nCoV, Treatment, Medicine, Therapy, Intervention, Drug, Medications, and Cure. All the relevant articles were collected from December 2019 to July 2020. RESULTS: We included 58 studies including 38 articles (eleven reviews, ten editorial documents, three case reports, one mix method, one cohort study), and 19 published clinical trials. Review of studies showed that Lopinavir/Ritonavir (n=16), Remdesivir (n=13), Convalescent plasma (n=11), Chloroquine (n=11), Ribavirin (n=9), Hydroxychloroquine sulfate (n=8), Traditional Chinese Medicine (TCM) (n=8), and Arbidol (n=7), were the most frequently therapies used to treat COVID-19 patients. CONCLUSION: In the absence of definitive treatment protocols, recently proposed approaches have appeared to be an effective therapy for accelerating the recovery of COVID-19 patients. Some of these treatments may have been in the early stages of testing. However, future preclinical and clinical trials are warranted to validate findings.

Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021).

PURPOSE: This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19. METHODS: The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation. RESULTS: The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D3 should not be used in COVID-19 routine care. CONCLUSION: For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.

Current treatment strategies for COVID­19 (Review).

The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID­19). To date, there is no specific therapy established to treat COVID­19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS­CoV­2 in humans. For the present review, >100 publications on therapeutic agents for COVID­19, including in vitro and in vivo animal studies, case reports, retrospective analyses and meta­analyses were retrieved from PubMed and analyzed, and promising therapeutic agents that may be used to combat SARS­CoV­2 infection were highlighted. Since the outbreak of COVID­19, different drugs have been repurposed for its treatment. Existing drugs, including chloroquine (CQ), its derivative hydroxychloroquine (HCQ), remdesivir and nucleoside analogues, monoclonal antibodies, convalescent plasma, Chinese herbal medicine and natural compounds for treating COVID­19 evaluated in experimental and clinical studies were discussed. Although early clinical studies suggested that CQ/HCQ produces antiviral action, later research indicated certain controversy regarding their use for treating COVID­19. The molecular mechanisms of these therapeutic agents against SARS­CoV2 have been investigated, including inhibition of viral interactions with angiotensin­converting enzyme 2 receptors in human cells, viral RNA­dependent RNA polymerase, RNA replication and the packaging of viral particles. Potent therapeutic options were reviewed and future challenges to accelerate the development of novel therapeutic agents to treat and prevent COVID­19 were acknowledged.

14-3-3ζ: A suppressor of inflammatory arthritis.

Inflammatory arthritis (IA) is a common disease that affects millions of individuals worldwide. Proinflammatory events during IA pathogenesis are well studied; however, loss of protective immunity remains underexplored. Earlier, we reported that 14-3-3zeta (ζ) has a role in T-cell polarization and interleukin (IL)-17A signal transduction. Here, we demonstrate that 14-3-3ζ knockout (KO) rats develop early-onset severe arthritis in two independent models of IA, pristane-induced arthritis and collagen-induced arthritis. Arthritic 14-3-3ζ KO animals showed an increase in bone loss and immune cell infiltration in synovial joints. Induction of arthritis coincided with the loss of anti-14-3-3ζ antibodies; however, rescue experiments to supplement the 14-3-3ζ antibody by passive immunization did not suppress arthritis. Instead, 14-3-3ζ immunization during the presymptomatic phase resulted in significant suppression of arthritis in both wild-type and 14-3-3ζ KO animals. Mechanistically, 14-3-3ζ KO rats exhibited elevated inflammatory gene signatures at the messenger RNA and protein levels, particularly for IL-1ß. Furthermore, the immunization with recombinant 14-3-3ζ protein suppressed IL-1ß levels, significantly increased anti-14-3-3ζ antibody levels and collagen production, and preserved bone quality. The 14-3-3ζ protein increased collagen expression in primary rat mesenchymal cells. Together, our findings indicate that 14-3-3ζ causes immune suppression and extracellular remodeling, which lead to a previously unrecognized IA-suppressive function.

Effect of postpartum collection time and colostrum quality on passive transfer of immunity, performance, and small intestinal development in preweaning calves.

This study evaluated the effects of postpartum collection time and quality of colostrum fed to calves on the failure of passive transfer, growth, and small intestine development in the first 5 wk of life. Newborn calves (Holstein-Friesian × Jersey) were identified at birth and collected either early (E; within 12 h postpartum; n = 20) or late (L; 18-24 h postpartum; n = 20) and fed either high-quality colostrum [HQC, first milking colostrum with Brix% = 23 ± standard deviation (SD) 2] or low-quality colostrum (LQC, mixed colostrum and transition milk with Brix% = 12 ± 1) to create 4 treatments: E-HQC, E-LQC, L-HQC, and L-LQC (n = 10/treatment). After collection, calves (body weight = 32.3 ± 4.6 kg/calf) were fed either HQC or LQC (7.5% of their arrival body weight per feed) for the first 3 (L calves) or 4 feedings (E calves). All calves were then managed and fed similarly using automatic feeders which recorded individual intake of milk replacer and calf starter. Blood samples were taken at d 1 (after collection from dams but before colostrum feeding), 4, 14, and 35 of age to analyze selected metabolites. All calves were killed at d 35 ± 2 of age and histomorphology of duodenum, jejunum, and ileum was evaluated. At collection, 75% of E calves and 58% of L calves had serum total protein ≤52 g/L. At d 4 of age, calves fed HQC had greater serum total protein than calves fed LQC; however, failure of passive transfer (serum total protein ≤52 g/L) incidence did not differ between HQC and LQC. Collection time did not affect the scouring duration, but the amount of electrolyte used to treat sick calves was lower in L versus E calves, whereas feeding HQC versus LQC lowered both the scouring duration and electrolyte use to treat sick calves. Calves fed HQC had a greater total surface area of the duodenum (+23%) and jejunum (+17%) compared with LQC calves. Duodenal crypts were deeper in E-LQC calves than E-HQC and L-HQC calves, whereas L-LQC calves were intermediate. Villus height to crypt depth ratio in duodenum, jejunum, and ileum was greater in HQC than LQC calves. A trend toward greater average daily gain was observed in HQC versus LQC calves (667 vs. 590 g/d) but the average daily gain was not influenced by collection time. Serum IGF-1 at d 4 was higher in HQC versus LQC calves and this might have contributed to greater average daily gain and small intestine development. Calves fed HQC had higher feed conversion ratios (FCR; total body weight gain/total dry matter intake) compared with LQC calves, and L calves had higher FCR compared with E calves. In conclusion, in comparison to feeding LQC, feeding HQC reduced the scouring duration, enhanced surface area of duodenum and jejunum, and improved FCR during the first 5 wk of calf age. Postpartum collection time of calves did not affect small intestine development, but L calves had higher FCR and required a lesser volume of electrolytes to treat scours compared with E calves during the first 35 d of life.

Prevalence of failure of passive transfer of immunity in dairy calves in a Mediterranean pasture-based production system of the south-west region of Western Australia.

The objective of this study was to estimate the prevalence of failure of passive transfer of immunity (FPTI) in dairy calves in the south-west region of Western Australia herds. A cross-sectional study was conducted in 26/140 dairy farms and serum samples were collected from 495 healthy 2-7 day-old calves. A radial immunodiffusion (RID) test was used to determine the concentration of serum IgG and calves were classified as having FPTI if the IgG concentration was less than 10 mg/mL. Estimation of FPTI was also assessed using two indirect methods using serum total protein (STP) and a brix refractometer. The estimated prevalence of FPTI was found to be 8.7% (43 calves out of 495) by RID with the concentration of IgG ranging between 0 and 6.2 mg/ml. The STP was found to vary from 46 to 96 mg/mL and using a cut-off point of 55 mg/mL the calf level prevalence was estimated as 7.1% (33 calves). Using the brix refractometer, the prevalence was found to be 13.1% (65 calves) with the refractometer reading ranging 6-14% of IgG. In the present study there was no association between calf-level factors (age, sex and breed) and FPTI. There was a higher correlation of the RID test results and the STP results compared to the RID and brix refractometer results. It is concluded that the prevalence of FPTI in dairy calves in the south-west region of Western Australia is low (8.7%) and the brix refractometer is not a reliable indirect method for determining passive transfer of immunity to calves.

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia.

HI, a fusion protein that consists of the alpha-toxin (Hla) and the N2 domain of iron surface determinant B (IsdB), is one of the antigens in the previously reported S. aureus vaccine rFSAV and has already entered phase II clinical trials. Previous studies revealed that HI is highly immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in HI-mediated protection. In this study, we further investigated the protective efficacy of immunization with HI plus four different adjuvants in a mouse bacteremia model. Results showed that HI-mediated protection was altered in response to different adjuvants. Using antisera from immunized mice, we identified seven B-cell immunodominant epitopes on Hla and IsdB, including 6 novel epitopes (Hla1-18, Hla84-101, Hla186-203, IsdB342-359, IsdB366-383, and IsdB384-401). The immunodominance of B-cell epitopes, total IgG titers and the levels of IFN-γ and IL-17A from mice immunized with HI plus different adjuvants were different from each other, which may explain the difference in protective immunity observed in each immunized group. Thus, our results indicate that adjuvants largely affected the immunodominance of epitopes and the protective efficacy of HI, which may guide further adjuvant screening for vaccine development and optimization.