North and south united to conquer viral diarrheas using innovative passive immunity strategies

My fortuitous journey to Argentina began 22 years ago in 1987 when I was invited by Dr Alejandro Schudel, then Director of Virology at INTA, Castelar, to visit Argentina to initiate a joint collaboration. The topic was «Rotavirus infections in calves: development and evaluation of maternal vaccines for passive immunity in calves». Passive immunity and enteric viral infections in swine and cattle were two of my major research interests at the Food Animal Health Research Program, Ohio Agricultural Research and Development Center (OARDC), The Ohio State University (OSU) in the USA. At the time, calf diarrhea was a critical problem in both beef and dairy calves, but the major causes were undefined. Our goals were first to identify the dominant pathogens in the field associated with calf diarrhea and deaths and second to develop methods for their prevention and control. To accomplish these goals, we addressed each of the following key questions in collaborative studies conducted in Argentina (INTA) and the USA (OARDC/The Ohio State University).Academia Nacional de Agronomía y Veterinari

Rotaviruses: Zoonotic potential and adaptation to new hosts

Group A rotaviruses are a leading cause of dehydrating diarrhea in children and also cause diarrhea in young animals worldwide.Academia Nacional de Agronomía y Veterinari

North and south united to conquer viral diarrheas using innovative passive immunity strategies

My fortuitous journey to Argentina began 22 years ago in 1987 when I was invited by Dr Alejandro Schudel, then Director of Virology at INTA, Castelar, to visit Argentina to initiate a joint collaboration. The topic was «Rotavirus infections in calves: development and evaluation of maternal vaccines for passive immunity in calves». Passive immunity and enteric viral infections in swine and cattle were two of my major research interests at the Food Animal Health Research Program, Ohio Agricultural Research and Development Center (OARDC), The Ohio State University (OSU) in the USA. At the time, calf diarrhea was a critical problem in both beef and dairy calves, but the major causes were undefined. Our goals were first to identify the dominant pathogens in the field associated with calf diarrhea and deaths and second to develop methods for their prevention and control. To accomplish these goals, we addressed each of the following key questions in collaborative studies conducted in Argentina (INTA) and the USA (OARDC/The Ohio State University).Academia Nacional de Agronomía y Veterinari

Rotaviruses: Zoonotic potential and adaptation to new hosts

Group A rotaviruses are a leading cause of dehydrating diarrhea in children and also cause diarrhea in young animals worldwide.Academia Nacional de Agronomía y Veterinari

No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2

The emergence and outbreak of a newly discovered acute respiratory disease in Wuhan, China, has affected greater than 40,000 people, and killed more than 1,000 as of Feb. 10, 2020. A new human coronavirus, SARSCoV- 2, was quickly identified, and the associated disease is now referred to as coronavirus disease discovered in 2019 (COVID-19) (https://globalbiodefense. com/novel-coronavirus-covid-19-portal/)

The Relative Odds of Progressing by Structural and Functional Tests in Glaucoma.

PurposeThe purpose of this study was to evaluate the effect of disease severity and number of tests acquired during follow-up on the relative odds of identifying progression by structural or functional tests in glaucoma.MethodsThis was an observational cohort study involving 462 eyes of 305 patients with glaucoma and 62 eyes of 49 healthy subjects. Glaucoma patients and healthy subjects were followed for an average of 3.6 ± 0.9 and 3.8 ± 0.9 years, with a median (interquantile range) of 8 (6-9) and 7 (6-8) visits, respectively. At each visit, subjects underwent visual field assessment with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) evaluation by spectral-domain optical coherence tomography (SD-OCT). Slopes of change in SAP mean sensitivity and OCT RNFL thickness over time were estimated by linear regression using progressively cumulative visits over time. Cutoff values for age-related expected rates of change for each test were obtained from the healthy group. Progression by SD-OCT and/or SAP was determined if the slope of change was statistically significant and also lower (faster) than the fifth percentile cutoff calculated from the healthy group. A generalized estimating equation logistic regression model was used to evaluate the relative odds of progressing by OCT versus SAP in glaucoma eyes.ResultsEyes with less severe disease at baseline had a higher chance of being detected as progressing by SD-OCT but not by SAP, whereas an increase in disease severity at baseline increased the chance that the eye would be detected as progressing by SAP but not SD-OCT. Each 1 dB higher MD was associated with a 5% increase in the odds of detecting progression by SD-OCT versus SAP (odds ratio = 1.05 per 1 dB; 95% confidence interval: 1.01-1.09; P = 0.005).ConclusionsThe ability to detect glaucoma progression by SAP versus SD-OCT is significantly influenced by the stage of disease. Our results may provide useful information for guiding clinicians on the relative utility of these tests for detecting change throughout the disease continuum

Rotavirus C: prevalence in suckling piglets and development of virus-like particles to assess the influence of maternal immunity on the disease development

International audienceAbstractRotavirus C (RVC) has been detected increasingly in humans and swine in different countries, including the US. It is associated with significant economic losses due to diarrheal disease in nursing piglets. In this study we aimed: (1) to determine the prevalence of RVC in healthy and diarrheic suckling piglets on US farms; and (2) to evaluate if maternal antibody (Ab) levels were associated with protection of newborn suckling piglets against RVC. There was a significantly higher prevalence (p = 0.0002) of litters with diarrhea born to gilts compared with those born to multiparous sows. Of 113 nursing piglet fecal samples tested, 76.1% were RVC RNA positive. Fecal RVC RNA was detected in significantly (p = 0.0419) higher quantities and more frequently in piglets with diarrhea compared with healthy ones (82.5 vs. 69.9%). With the exception of the historic strain Cowden (G1 genotype), field RVC strains do not replicate in cell culture, which is a major impediment for studying RVC pathogenesis and immunity. To circumvent this, we generated RVC virus-like particles (VLPs) for Cowden (G1), RV0104 (G3) and RV0143 (G6) and used them as antigens in ELISA to detect swine RVC Abs in serum and milk from the sows. Using RVC-VLP Ab ELISA we demonstrated that sows with diarrheic litters had significantly lower RVC IgA and IgG Ab titers in milk compared to those with healthy litters. Thus, our data suggest that insufficient lactogenic protection provided by gilts plays a key role in the development of and the increased prevalence of clinical RVC disease

Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A

ABSTRACT Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic alphacoronavirus. In the United States, highly virulent PEDV strains cause between 80 and 100% mortality in suckling piglets and are rapidly transmitted between animals and farms. To study the genetic factors that regulate pathogenesis and transmission, we developed a molecular clone of PEDV strain PC22A. The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo . Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. Using reverse genetics, we removed open reading frame 3 (ORF3) and replaced this region with a red fluorescent protein (RFP) gene to generate icPEDV-ΔORF3-RFP. icPEDV-ΔORF3-RFP replicated efficiently in vitro and in vivo , was efficiently transmitted among pigs, and produced lethal disease outcomes. However, the diarrheic scores in icPEDV-ΔORF3-RFP-infected pigs were lower than those in wild-type-virus- or icPEDV-infected pigs, and the virus formed smaller plaques than those of PC22A. Together, these data describe the development of a robust reverse-genetics platform for identifying genetic factors that regulate pathogenic outcomes and transmission efficiency in vivo , providing key infrastructural developments for developing and evaluating the efficacy of live attenuated vaccines and therapeutics in a clinical setting. IMPORTANCE Porcine epidemic diarrhea virus (PEDV) emerged in the United States in 2013 and has since killed 10% of U.S. farm pigs. Though the disease has been circulating internationally for decades, the lack of a rapid reverse-genetics platform for manipulating PEDV and identifying genetic factors that impact transmission and virulence has hindered the study of this important agricultural disease. Here, we present a DNA-based infectious-clone system that replicates the pathogenesis of circulating U.S. strain PC22A both in vitro and in piglets. This infectious clone can be used both to study the genetics, virulence, and transmission of PEDV coronavirus and to inform the creation of a live attenuated PEDV vaccine

Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets

International audienceAbstractVitamin A (VA) has pleiotropic effects on the immune system and is critical for mucosal immune function and intestinal lymphocyte trafficking. We hypothesized that oral VA supplementation of porcine epidemic diarrhea virus (PEDV)-infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV challenge. Gilts received daily oral retinyl acetate (30 000 IU) starting at gestation day 76 throughout lactation. At 3–4 weeks pre-partum, VA-supplemented (PEDV + VA) and non-supplemented (PEDV) gilts were PEDV or mock inoculated (mock + VA and mock, respectively). PEDV + VA gilts had decreased mean PEDV RNA shedding titers and diarrhea scores. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3–5 days post-partum. The survival rate of PEDV + VA litters was 74.2% compared with 55.9% in PEDV litters. Mock and mock + VA litter survival rates were 5.7% and 8.3%, respectively. PEDV + VA gilts had increased PEDV IgA antibody secreting cells and PEDV IgA antibodies in serum pre-partum and IgA+β7+ (gut homing) cells in milk post piglet challenge compared with PEDV gilts. Our findings suggest that oral VA supplementation may act as an adjuvant during pregnancy, enhancing maternal IgA and lactogenic immune protection in nursing piglets

Characterization and Prevalence of a New Porcine Calicivirus in Swine, United States

Real-time reverse transcription PCR revealed that new St-Valerien–like porcine caliciviruses are prevalent (2.6%–80%; 23.8% overall) in finisher pigs in North Carolina. One strain, NC-WGP93C, shares 89.3%–89.7% genomic nucleotide identity with Canadian strains. Whether these viruses cause disease in pigs or humans or are of food safety concern requires further investigation