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Principal Investigator: Isaac Jonathan Krauss
Organization: BRANDEIS UNIVERSITY
Fiscal Year: 2019
Award: $124,644
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract
An estimated 2.3 billion people live at risk of infection by the Zika virus (ZIKV), a mosquito-borne flavivirus
that causes microcephaly in newborns, as well as eye- and neurological defects, and Guillain-Barre
syndrome in adults. Zika co-circulates in the same geographical region with the four serotypes of Dengue
virus, which is of concern for both Dengue and Zika vaccine development. Antibodies that develop in
response to Dengue can enhance Zika infection, and vice versa (Antibody-Dependent Enhancement,
ADE). A recently discovered class of antibodies has been found to exhibit less ADE; these antibodies
broadly and potently neutralize Zika and all four Dengue serotypes, and do so by binding to a quaternary
epitope at the interface between adjacent E glycoprotein subunits on the viral envelope. This envelope
dimer epitope (EDE) is a promising target for vaccine development.
The goal of this exploratory R21 project is to discover glycopeptides that are good structural mimics of
the EDE on ZIKV. Such molecules, when used as vaccine immunogens, should stimulate a broadly
neutralizing antibody response that is protective against ZIKV, while avoiding ADE effects. The Krauss
lab will use its directed evolution technology to scaffold the carbohydrate and peptide components of the
EDE into arrangements that enable strong recognition by EDE antibodies, producing EDE mimics. Two
further types of studies will then determine which among these glycopeptide “hits” are best for future
immunogenicity studies. The Sarathy and Barrett labs with determine whether selected glycopeptides
compete with ZIKV for binding to the EDE antibodies, whereas the Wilson lab will determine structures
of glycopeptide-antibody complexes to determine whether glycopeptides bind to the antibodies through
ZIKV-like contacts.
Terms: <0-4 weeks old><21+ years old><AIDP><ATGN><Acute Autoimmune Neuropathy><Acute Infective Polyneuritis><Acute Inflammatory Demyelinating Polyradiculoneuropathy><Acute Inflammatory Polyneuropathy><Acute Inflammatory Polyradiculoneuropathy><Adult><Adult Human><Americas><Antibodies><Antibody Binding Sites><Antibody Response><Antibody Specificity><Antibody-Dependent Enhancement><Antigenic Determinants><Antigens><Antiviral Agents><Antiviral Drugs><Antivirals><Area><Assay><Autoimmune><Autoimmune Process><Bacteriophages><Binding><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><Birth Defects><Blood Circulation><Bloodstream><Breakbone Fever Virus><Carbohydrates><Cell Body><Cells><Circulation><Clinical Treatment Moab><Complex><Congenital Abnormality><Congenital Anatomic Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><DENV infection><DENV vaccine><Dangerousness><Data><Defect><Dengue><Dengue Fever><Dengue Infection><Dengue Vaccine><Dengue Virus><Dengue virus infection><Dengue virus vaccine><Development><Directed Molecular Evolution><Disease><Disorder><Elements><Envelope Protein><Epitopes><Exhibits><Eye><Eyeball><Fc Receptor><Flavivirus><Future><General Viruses><Generalized Growth><Geographic Area><Geographic Locations><Geographic Region><Geographical Location><Glycans><Glycopeptides><Glycoproteins><Goals><Group B Arbovirus><Growth><Guillain-Barré Syndrome><Guillaine-Barre Syndrome><Hearing Loss><Hu-mABs><Human><Hypoacuses><Hypoacusis><Impairment><Infection><Landry's paralysis><Landry-Guillain-Barre Syndrome><Libraries><Mediating><Messenger RNA><Microcephaly><Modern Man><Molecular Configuration><Molecular Conformation><Molecular Interaction><Molecular Stereochemistry><Monoclonal Antibodies><Muscle Weakness><Muscular Weakness><Neurologic><Neurological><Newborn Infant><Newborns><PBMC><Palsy><Paralysed><Paratopes><Patients><Peptide Fragments><Peptides><Peripheral Blood Mononuclear Cell><Phages><Plegia><Polysaccharides><Proteins><Public Health><Reaction><Research Design><Roentgen Rays><Safety><Serologic><Serological><Serotyping><Side><Structure><Study Type><Techniques><Technology><Tissue Growth><Vaccines><Viral><Viral Gene Products><Viral Gene Proteins><Viral Proteins><Virion><Virus><Virus Particle><X-Radiation><X-Rays><X-Rays Radiation><Xrays><Yeasts><ZIKA><ZIKV><ZIKV infection><Zika Virus><Zika vaccine><Zika virus infection><Zika virus vaccine><acute idiopathic polyneuritis><acute post-infectious polyneuropathy><acute postinfectious polyneuropathy><adulthood><anti-viral agents><anti-viral drugs><anti-virals><antibody combining site><antibody receptor><bacterial virus><base><breakbone fever><combat><conformation><conformational state><dengue viral infection><design><designing><develop a vaccine><development of a vaccine><developmental><dimer><directed evolution><dysfunctional hearing><env Antigens><env Gene Products><env Polyproteins><env Protein><geographic site><hazard><hearing defect><hearing deficit><hearing difficulty><hearing disability><hearing dysfunction><hearing impairment><high risk><humAbs><human mAbs><human monoclonal antibodies><human monoclonals><immunogen><immunogenicity><infection risk><mAbs><mRNA><micrencephaly><microencephaly><mosquito-borne><mosquitoborne><mouse model><murine model><mutant><neutralizing antibody><new vaccines><newborn child><newborn children><next generation vaccines><novel vaccines><ontogeny><paralysis><paralytic><particle><peptide aminoacid sequence><peptide sequence><prenatal><protein aminoacid sequence><response><scaffold><scaffolding><study design><unborn><uptake><vaccine development><vaccine formulation><virus protein><zika infection><zika viral infection><zikav>