To do so, many vaccines contain viral molecules called glycoproteins, which are specific to each type of virus. Vaccines train the immune system to recognize a specific virus or bacterium so that the body can be better prepared against these harmful agents. coli HEK293F Lemo21 computational biology human immunology inflammation systems biology virus. This work demonstrates that antigen-displaying protein nanoparticles can be designed from scratch, and provides a systematic way to investigate the influence of antigen presentation geometry on the immune response to vaccination.ī lymphocytes BL21 E. Electron microscopy and antibody binding experiments demonstrated that the designed nanoparticles presented antigenically intact prefusion HIV-1 Env, influenza hemagglutinin, and RSV F trimers in the predicted geometries. Trimers that experimentally adopted their designed configurations were incorporated as components of tetrahedral, octahedral, and icosahedral nanoparticles, which were characterized by cryo-electron microscopy and assessed for their ability to present viral glycoproteins. We first de novo designed trimers tailored for antigen fusion, featuring N-terminal helices positioned to match the C termini of the viral glycoproteins. To enable a new generation of anti-viral vaccines, we designed self-assembling protein nanoparticles with geometries tailored to present the ectodomains of influenza, HIV, and RSV viral glycoprotein trimers. Multivalent presentation of viral glycoproteins can substantially increase the elicitation of antigen-specific antibodies. 11 Howard Hughes Medical Institute, University of Washington, Seattle, United States.10 Center for Advanced Mathematics in Energy Research Applications, Computational Research Division, Lawrence Berkeley Laboratory, Berkeley, United States.9 Amsterdam UMC, Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.8 Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, United States.7 Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, United States.
6 Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, United States.5 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.4 International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, United States.3 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.2 Institute for Protein Design, University of Washington, Seattle, United States.1 Department of Biochemistry, University of Washington, Seattle, United States.
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