6 research outputs found
Feasibility of polyclonal avian immunoglobulins (IgY) as prophylaxis against human norovirus infection
Background: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. Methods: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. Results: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:221 (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. Conclusions: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.Instituto de VirologĂaFil: Artman, Chad. Scaled Microbiomics; Estados UnidosFil: Idegwu, Nnebuefe. Scaled Microbiomics; Estados UnidosFil: Brumfield, Kyle D. College Park Campus. University of Maryland. Maryland Pathogen Research Institute; Estados UnidosFil: Brumfield, Kyle D. College Park Campus. University of Maryland. University of Maryland Institute for Advanced Computer Studies; Estados UnidosFil: Lai, Ken. University of Saskatchewan. Vaccine and Infectious Disease Organization; CanadáFil: Hauta, Shirley. University of Saskatchewan. Vaccine and Infectious Disease Organization; CanadáFil: Falzarano, Darryl. University of Saskatchewan. Vaccine and Infectious Disease Organization; CanadáFil: Falzarano, Darryl. University of Saskatchewan. Western College of Veterinary Medicine. Department of Veterinary Microbiology; CanadáFil: Parreño, Gladys Viviana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de TecnologĂa Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Geyer, James D. University of Alabama. College of Community Health Science. Institute for Rural Health Research; Estados UnidosFil: Goepp, Julius G. Scaled Microbiomics; Estados Unido
Avian antibodies (IgY) targeting spike glycoprotein of severe acute respiratory syndrome coronavirus 2Â (SARS-CoV-2) inhibit receptor binding and viral replication.
BackgroundThe global pandemic of Coronavirus infectious disease 2019 (COVID-19), caused by SARS-CoV-2, has plunged the world into both social and economic disarray, with vaccines still emerging and a continued paucity of personal protective equipment; the pandemic has also highlighted the potential for rapid emergence of aggressive respiratory pathogens and the need for preparedness. Avian immunoglobulins (IgY) have been previously shown in animal models to protect against new infection and mitigate established infection when applied intranasally. We carried out a proof-of-concept study to address the feasibility of using such antibodies as mucosally-applied prophylaxis against SARS-CoV-2.MethodsHens were immunized with recombinant S1 spike glycoprotein of the virus, and the resulting IgY was evaluated for binding specificity, inhibition of glycoprotein binding to angiotensin converting enzyme-2 (ACE2) protein (the requisite binding site for the virus), and inhibition of viral replication in Vero cell culture.ResultsTiters of anti-S1 glycoprotein IgY were evident in yolks at 14 days post-immunization, peaking at 21 days, and at peak concentrations of 16.8 mg/ml. IgY showed strong and significant inhibition of S1/ACE2 binding interactions, and significantly inhibited viral replication at a concentration of 16.8 mg/ml. Four weeks' collection from eggs of two hens produced a total of 1.55 grams of IgY.ConclusionsIn this proof-of-concept study we showed that avian immunoglobulins (IgY) raised against a key virulence factor of the SARS-CoV-2 virus successfully inhibited the critical initial adhesion of viral spike glycoproteins to human ACE2 protein receptors and inhibited viral replication in vitro, in a short period using only two laying hens. We conclude that production of large amounts of IgY inhibiting viral binding and replication of SARS-CoV-2 is feasible, and that incorporation of this or similar material into an intranasal spray and/or other mucosal protecting products may be effective at reducing infection and spread of COVID-19
A Taxonomy-Agnostic Approach to Targeted Microbiome Therapeutics—Leveraging Principles of Systems Biology
The study of human microbiomes has yielded insights into basic science, and applied therapeutics are emerging. However, conflicting definitions of what microbiomes are and how they affect the health of the “host” are less understood. A major impediment towards systematic design, discovery, and implementation of targeted microbiome therapeutics is the continued reliance on taxonomic indicators to define microbiomes in health and disease. Such reliance often confounds analyses, potentially suggesting associations where there are none, and conversely failing to identify significant, causal relationships. This review article discusses recent discoveries pointing towards a molecular understanding of microbiome “dysbiosis” and away from a purely taxonomic approach. We highlight the growing role of systems biological principles in the complex interrelationships between the gut microbiome and host cells, and review current approaches commonly used in targeted microbiome therapeutics, including fecal microbial transplant, bacteriophage therapies, and the use of metabolic toxins to selectively eliminate specific taxa from dysbiotic microbiomes. These approaches, however, remain wholly or partially dependent on the bacterial taxa involved in dysbiosis, and therefore may not capitalize fully on many therapeutic opportunities presented at the bioactive molecular level. New technologies capable of addressing microbiome-associated diseases as molecular problems, if solved, will open possibilities of new classes and categories of targeted microbiome therapeutics aimed, in principle, at all dysbiosis-driven disorders
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Patient- and Community-Level Sociodemographic Characteristics Associated with Emergency Department Visits for Childhood Injury
ObjectiveTo examine pediatric emergency department (ED) visits over 5 years, trends in injury severity, and associations between injury-related ED visit outcome and patient and community-level sociodemographic characteristics.Study designRetrospective analysis of administrative data provided to the Pediatric Emergency Care Applied Research Network Core Data Project, 2004-2008. Home addresses were geocoded to determine census block group and associated sociodemographic characteristics. Maximum Abbreviated Injury Scale severity and Severity Classification System scores were calculated. Generalized estimating equations were used to test for associations between sociodemographic characteristics and admission or transfer among injury-related ED visits.ResultsOverall ED visits and injury-related visits increased from 2004 to 2008 at study sites. Of 2,833676 successfully geocoded visits, 700,821 (24.7%) were injury-related. The proportion of higher severity injury-related visits remained consistent. Nearly 10% of injury-related visits resulted in admission or transfer each year. After adjusting for age, sex, payer, and injury severity, odds of admission or transfer were lower among minority children and children from areas with moderate and high prevalence of poverty.ConclusionsPediatric injury-related ED visits to included sites increased over the study period while injury severity, anticipated resource utilization, and visit outcomes remained stable, with low rates of admission or transfer. Sociodemographic differences in injury-related visits and ED disposition were apparent. ED-based injury surveillance is essential to understand disparities, inform targets for prevention programs, and reduce the overall burden of childhood injuries