The goal of this project is to generate an improved HIV-1 vaccine immunogen geared toward antibody responses by engineering an HIV-1 Envelope glycoprotein (Env) trimeric complex that is stabilized in its functionally relevant conformation by application of Avatar's proprietary dityrosine protein stabilization technology. The project breaks into two Specific Aims: (i) identification of constructs in which dityrosine crosslinks form to stabilize Env complexes, and (ii) antigenic and physiochemical analyses of DT stabilized Env trimers identified in (i) above, specifically by antigenic and Biacore analyses, and amino acid, mass spectrometric, and size exclusion chromatographic analyses, respectively. The project will be executed in collaboration between Avatar Medical, LLC and the International AIDS Vaccine Initiative. IAVI will design the constructs for evaluation, and Avatar will generate the DNA constructs required for protein construct expression and evaluation. Avatar and IAVI will jointly generate and purify the protein. IAVI will conduct the antigenic analyses, and Avatar will conduct biophysical characterization, including conducting amino acid and size exclusion chromatographic analysis, and overseeing the mass spectrometric analysis outsourced to Creative Proteomics, Inc.
Public Health Relevance: The goal of this project is to generate an injectable vaccine product that will trigger immune responses that protect against infection by the Human Immunodeficiency Virus by taking a novel approach to protein engineering. The product will specifically trigger production of antibodies in vaccinated individuals that will bind to, and neutralize the virus when it enters the body. The goal is to develop a product that triggers production of antibodies that will bind to any HIV particle, and therefore protect vaccinated individuals, regardless of the strain of virus they are exposed to.
Thesaurus Terms: Adme Study;Aids Antibodies;Aids Vaccines;Aids Virus;Atgn;Absorption, Distribution, Metabolism, And Excretion Study;Acquired Immune Deficiency Syndrome Virus;Acquired Immunodeficiency Syndrome Virus;Affinity;Amino Acids;Antibody Formation;Antibody Production;Antibody Response;Antigenic Determinants;Antigens;Assay;Binding;Binding (Molecular Function);Binding Determinants;Bioassay;Biologic Assays;Biological Assay;Cell Line;Cellline;Collaborations;Complex;Dna;Deoxyribonucleic Acid;Development;Domestic Rabbit;Elisa;Electrons;Engineering;Envelope Protein;Enzyme-Linked Immunosorbent Assay;Epitopes;Evaluation;Exclusion;Fluorescence;General Viruses;Genetics-Mutagenesis;Glycoproteins;Goals;Hiv;Hiv Antibodies;Hiv Envelope Glycoprotein Gp120;Hiv Envelope Protein Gp120;Hiv Env Protein Gp120;Hiv-1;Hiv-Associated Antibodies;Hiv-I;Hiv1;Htlv-Iii;Htlv-Iii Antibodies;Htlv-Iii Gp120;Htlv-Iii-Lav Antibodies;Human Immunodeficiency Virus Type 1;Human Immunodeficiency Viruses;Human T-Cell Leukemia Virus Type Iii;Human T-Cell Lymphotropic Virus Type Iii;Human T-Lymphotropic Virus Type Iii;Human T-Lymphotropic Virus Type Iii Antibodies;Human Immunodeficiency Virus 1;Immune Response;Individual;Infection;Injectable;International Aids;L-Isomer Phenylalanine;L-Phenylalanine;L-Tyrosine;L-Isomer Tyrosine;Lav Antibodies;Lav-Htlv-Iii;Ligands;Lymphadenopathy-Associated Antibodies;Lymphadenopathy-Associated Virus;Mediating;Medical;Molecular Configuration;Molecular Conformation;Molecular Interaction;Molecular Sieve Chromatography;Molecular Stereochemistry;Mutagenesis;Mutagenesis Molecular Biology;Negative Beta Particle;Negatrons;Oryctolagus Cuniculus;Phase;Phenylalanine;Point Mutation;Position;Positioning Attribute;Preparation;Process;Production;Protein Engineering;Proteins;Proteomics;Rabbits;Rabbits Mammals;Reaction;Receptor Protein;Resolution;Sos;Sos Proteins;Sos Exchange Factor;Sensitivity And Specificity;Site;Size Exclusion Chromatography;Son Of Sevenless Proteins;Strains Cell Lines;Structure;Surface;Technology;Tyrosine;Vaccinated;Vaccines;Viral;Virus;Virus-Hiv;Work;Aminoacid;Antibody Biosynthesis;Base;Bityrosine;Conformation;Conformational State;Cross-Link;Crosslink;Cultured Cell Line;Design And Construct;Design And Construction;Developmental;Dityrosine;Env Antigens;Env Gene Products;Env Glycoproteins;Env Polyproteins;Env Protein;Gene Product;Genetic Protein Engineering;Gp120;Gp120 Env Glycoprotein;Gp120(Hiv);Host Response;Human T Cell Leukemia Virus Iii;Human T Lymphotropic Virus Iii;Immunogen;Immunogenicity;Immunoglobulin Biosynthesis;Immunoresponse;Improved;Neutralizing Antibody;New Approaches;Novel Approaches;Novel Strategies;Novel Strategy;O,O-Dityrosine;Para-Tyrosine;Particle;Product Development;Programs;Protein Structure;Receptor;Receptor Binding;Son Of Sevenless Protein
