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Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 11, Iss 7, p e0005721 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science, 2017.
-
Abstract
- Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.<br />Author summary Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations following secondary heterotypic dengue virus (DENV) infections. DENV infects almost 400 million people annually and there are currently no licensed therapies to treat DENV-induced disease. DHF and DSS are mediated by serotype cross-reactive antibodies that facilitate antibody dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on surrounding cells. ADE results in a heightened immune response and in part mediates the pathogenesis of secondary DENV infections. Researchers have developed an animal model of ADE-induced severe DENV in which anti-DENV2 antibodies genetically engineered to eliminate FcR binding have therapeutic and prophylactic efficacy. Our study suggests that avian-derived anti-DENV2 IgY, without genetic modification, is able to provide protection both in vitro and against a lethal DENV challenge in vivo. IgY has emerged as an attractive, alternative therapeutic antibody because of its biological characteristics that enable it to prevent some of the adverse reactions that mammalian antibodies have when used for human immunotherapy. Specifically, IgY does not bind to mammalian complement or rheumatoid factor and has proven to be very safe for human consumption. Without modification, anti-DENV2 IgY can be rapidly produced and may serve as a good therapeutic option to treat dengue worldwide.
- Subjects :
- 0301 basic medicine
Serotype
RNA viruses
Proteomics
Viral Diseases
Physiology
Microarrays
Dengue virus
medicine.disease_cause
Pathology and Laboratory Medicine
Antibodies, Viral
Biochemistry
Epitope
Dengue fever
Dengue Fever
Epitopes
Mice
Viral Envelope Proteins
Immune Physiology
Geese
Medicine and Health Sciences
Enzyme-Linked Immunoassays
Mice, Knockout
Immune System Proteins
biology
lcsh:Public aspects of medicine
Vaccination
Nucleic acids
Infectious Diseases
Bioassays and Physiological Analysis
Medical Microbiology
Viral Pathogens
Viruses
Female
Antibody
Pathogens
Research Article
Neglected Tropical Diseases
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
030106 microbiology
Immunology
Immunoglobulins
Cross Reactions
Research and Analysis Methods
Microbiology
Peptide Mapping
Antibodies
Cell Line
03 medical and health sciences
medicine
Genetics
Animals
Humans
Antibody-dependent enhancement
Severe Dengue
Immunoassays
Molecular Biology Techniques
Molecular Biology
Microbial Pathogens
Flaviviruses
Gene Mapping
Public Health, Environmental and Occupational Health
Organisms
Biology and Life Sciences
Proteins
lcsh:RA1-1270
Dengue Virus
medicine.disease
Tropical Diseases
Virology
Antibodies, Neutralizing
Antibody-Dependent Enhancement
Alternative Splicing
030104 developmental biology
Epitope mapping
RNA processing
biology.protein
Immunologic Techniques
RNA
Gene expression
Epitope Mapping
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 11
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....32b3227e06adf4d21780a821723875bf