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Principal Investigator: Peter D Kwong
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2021
Award: $2,127,279
Funding agency: National Institute of Allergy and Infectious Diseases
Based on our understanding of spike- or envelope-based mechanisms of humoral evasion, we are working to design envelope-based immunogens with these evading mechanisms disabled. Such modified immunogens with weakened defenses may elicit more broadly neutralizing antibodies. We have also devised protein scaffolding technologies, as a means of presenting structural mimics of the epitopes of broadly neutralizing antibodies to assist in their re-elicitation. Scaffolds can be non-homologous proteins, identified through structural searches of the entire Protein Data Bank (PDB). Alternatively, scaffolds can be homologous proteins, which are structurally similar, but antigenically distinct from the HIV-1 envelope glycoproteins. An alternative to scaffolding involves "resurfacing", where the surface of a molecule, not involved in eliciting a desired response, is altered between "prime" and "boost" phases of immunization. We have also begun to couple epitope mimics to highly immunogenic carrier proteins or to display epitope mimics in the context of self-assembling nanoparticles, which have substantially higher immunogenicity than monovalent or even trivalent immunogens.
In addition to such "designer immunogens", we have also been investigating how insights from B cell ontogeny of broadly neutralizing antibodies can identify difficult steps in the elicitation process, which might be influenced by immunization; such antibody-lineage based design seeks to exploit our understanding of the specific developmental processes that a target lineage requires to achieve neutralization - and to "re-elicit" similar antibodies in the general population through antibody-lineage based design.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Antibodies><Antigenic Determinants><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding Determinants><Binding Sites><COVID-19 virus><COVID19 virus><Carrier Proteins><Cell Ontogeny><Child><Child Youth><Children (0-21)><Clinical Trials><CoV-2><CoV2><Combining Site><Coupled><Cryo-electron Microscopy><Cryoelectron Microscopy><Developmental Process><Disabled Persons><Disabled Population><Electron Cryomicroscopy><Epitopes><Exposure to><General Population><General Public><Glycoproteins><HIV-1><HIV-1 vaccine><HIV-I><HIV1><HIV1 vaccine><Handicapped><Homologous Protein><Hospital Admission><Hospitalization><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><Immune><Immune response><Immunes><Immunization><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunostimulation><Influenza Virus><Knowledge><Malaria><Medicine><N-terminal><NH2-terminal><NMR Spectrometer><NMR Spectroscopy><Norovirus><Norwalk-like Viruses><Paludism><People with Disabilities><Peptides><Persons with Disabilities><Phase><Plasmodium Infections><Process><Protein Homolog><ProteinHomolog><Proteins><Reactive Site><Reagent><Respiratory syncytial virus><SARS corona virus 2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Scaffolding Protein><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Single Crystal Diffraction><Structure><Surface><Technology><Transplantation><Transport Protein Gene><Transport Proteins><Transporter Protein><Vaccine Design><Wuhan coronavirus><X Ray Crystallographies><X-Ray Crystallography><X-Ray Diffraction Crystallography><X-Ray/Neutron Crystallography><Xray Crystallography><base><coronavirus disease 2019 virus><cryo-EM><cryoEM><design><designing><disabled><disabled individual><disabled people><evaluate vaccines><hCoV19><host response><human pathogen><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><improved><individuals with disabilities><influenzavirus><insight><nCoV2><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><nuclear magnetic resonance spectroscopy><pathogen><protein data bank><protein databank><response><scaffold><scaffolding><tool><transplant><vaccine evaluation><vaccine screening><vaccine testing><youngster>