Scientific Core Two

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Marie  Pancera
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2024
Award: $493,694
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT
Broadly neutralizing antibodies are likely to be an important component of an HIV-1 vaccine. The HIV-1 Envelope
(Env) glycoprotein is the sole target of neutralizing antibodies and has been a focus of immunogen designs. Yet
diverse recombinant (rec) Envs do not display detectable binding to the inferred germline (gl) of certain bNAbs,
such as the VRC01-class bNAbs, which are the focus of our IPCAVD project. Rec Envs capable of binding
glVRC01 bNAbs have been designed and induced the production of glVRC01 bNAbs when used as
immunogens. In this IPCAVD, we propose to determine if self-amplifying (sa) mRNA expressing our germline-
targeting 426c.Mod.Core prime and HxB2.WT.Core boost immunogens, expressed either as secreted
nanoparticles (-C4b) or membrane-anchored (gp160ΔCT), will initiate the maturation of VRC01 B cell response
in humans. The Scientific Core Two will provide high quality reagents to Scientific Projects One and Two and
Scientific Core One of this IPCAVD as well as structural information on selected vaccine-elicited Mab of interest
in complex with their antigens, to delineate their epitopes. This information will help us to better understand the
B cell response elicited by the saRNA constructs compared to rec Env immunogens.

Terms: <Ab response><Antibodies><Antibody Formation><Antibody Production><Antibody Response><Antigenic Determinants><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Binding Determinants><Biochemical><C4 b><C4b><Clinical Treatment Moab><Complement 4b><Complement C4b><Complex><Cryo-electron Microscopy><Cryoelectron Microscopy><Crystallization><Cyclic GMP><ELISA><Electron Cryomicroscopy><Electron Microscopy Facility><Envelope Protein><Enzyme-Linked Immunosorbent Assay><Epitopes><Germ Lines><Glycoproteins><Guanosine Cyclic Monophosphate><HIV-1><HIV-1 vaccine><HIV-I><HIV1><HIV1 vaccine><Human><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><Immunization><In Vitro><KI mice><Knock-in Mouse><Mammalian Cell><Maps><Membrane><Messenger RNA><Methodology><Methods><Modern Man><Molecular Interaction><Monoclonal Antibodies><Production><RNA vaccine><RNA-based vaccine><Reagent><Recombinant Antibody><Recombinant Proteins><Recombinants><Resolution><Robot><Sarna><Single Crystal Diffraction><Structure><Universities><Vaccines><Validation><Washington><X Ray Crystallographies><X-Ray Crystallography><X-Ray Diffraction Crystallography><X-Ray/Neutron Crystallography><Xray Crystallography><antibody biosynthesis><cGMP><cryo-EM><cryoEM><cryogenic electron microscopy><design><designing><env Antigens><env Gene Products><env Glycoproteins><env Polyproteins><env Protein><enzyme linked immunoassay><immunogen><immunoglobulin biosynthesis><interest><knockin mice><mAbs><mRNA><mRNA vaccine><mRNA-based vaccine><manufacture><membrane structure><monoclonal Abs><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><protein complex><resolutions><response><validations>