Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence
Copyright policy )Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence
AbstractStabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.
- Amsterdam UMC Netherlands
- University of Amsterdam Netherlands
- UNIVERSITEIT VAN AMSTERDAM Netherlands
- Scripps Research Institute United States
- Duke Medical Center United States
ENV, 570, SUBTYPE-B, Science, 610, VACCINE, HIV Antibodies, Article, env Gene Products, GLYCAN SHIELD, Epitopes, DESIGN, MD Multidisciplinary, Consensus Sequence, CRYO-EM STRUCTURE, Animals, CELL, Neutralizing, AIDS Vaccines, Science & Technology, Q, env Gene Products, Human Immunodeficiency Virus, GERMLINE PRECURSORS, Antibodies, Neutralizing, Multidisciplinary Sciences, ANTIBODIES, HIV-1, Science & Technology - Other Topics, Macaca, Rabbits, Protein Multimerization, GLYCOPROTEIN COMPLEX, Human Immunodeficiency Virus
ENV, 570, SUBTYPE-B, Science, 610, VACCINE, HIV Antibodies, Article, env Gene Products, GLYCAN SHIELD, Epitopes, DESIGN, MD Multidisciplinary, Consensus Sequence, CRYO-EM STRUCTURE, Animals, CELL, Neutralizing, AIDS Vaccines, Science & Technology, Q, env Gene Products, Human Immunodeficiency Virus, GERMLINE PRECURSORS, Antibodies, Neutralizing, Multidisciplinary Sciences, ANTIBODIES, HIV-1, Science & Technology - Other Topics, Macaca, Rabbits, Protein Multimerization, GLYCOPROTEIN COMPLEX, Human Immunodeficiency Virus
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