Glycoantigen evolution targeting antibodies of the PGT 128 lineage

Document text

Principal Investigator: Isaac Jonathan Krauss
Organization: BRANDEIS UNIVERSITY
Fiscal Year: 2020
Award: $587,087
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary/Abstract
Extensive study of HIV+ individuals in recent years has brought to light many examples of antibodies that
can neutralize a broad range of HIV strains and protect against viral challenge in animal models of
infection. The portion of viral surface most commonly targeted by such antibodies is now known to be
the “high-mannose patch”: among patients producing broadly-neutralizing antibodies, 38% target this
one region of the virus. One of the most potent high mannose patch antibodies, PGT128, binds to a
particular arrangement of high-mannose glycans and conserved peptide residues. Our goal is to develop
vaccine immunogens which mimic this arrangement precisely and be used to elicit PGT128-like
antibodies.
Our approach will utilize unique directed evolution methods to develop glycoimmunogens in which
PGT128 epitope elements are correctly reconstituted. It is also possible that additional immunogens will
be required to correctly prime the immune response by stimulating germline precursors of PGT128.
Therefore, we will develop glycopeptides targeting both mature and germline PGT128 antibodies. In
collaboration with David Nemazee at Scripps, we will investigate the ability of these glycopeptides in
combination, to activate a germline PGT128 response that can mature into a response with broadly-
neutralizing PGT128-like specificity.

Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Affinity><Amino Acids><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Response><Antigenic Determinants><Antigens><Award><B blood cells><B cell><B cell repertoire><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Binding Determinants><Biophysics><Cell Body><Cell Culture Techniques><Cells><Clinical Treatment Moab><Collaborations><Complex><D-Mannose><Directed Molecular Evolution><Domestic Rabbit><Elements><Epitopes><Evaluation><Event><Evolution><Glycans><Glycopeptides><Goals><HIV><HIV Envelope Glycoprotein gp120><HIV Envelope Protein gp120><HIV Infections><HIV env Protein gp120><HTLV-III Infections><HTLV-III gp120><HTLV-III-LAV Infections><Health><Human><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Hybridomas><Immune response><Immunization><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunostimulation><Individual><Infection><KI mice><Knock-in><Knock-in Mouse><LAV-HTLV-III><Libraries><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca mulatta><Mannopyranose><Mannopyranoside><Mannose><Messenger RNA><Methods><Mice><Mice Mammals><Modern Man><Molecular Interaction><Monitor><Monoclonal Antibodies><Murine><Mus><Oryctolagus cuniculus><Patients><Peptides><Phase><Polysaccharides><Protocol><Protocols documentation><Rabbits><Rabbits Mammals><Regimen><Rhesus Macaque><Rhesus Monkey><Site><Specificity><Structure><Surface><Techniques><Testing><Vaccines><Variant><Variation><Viral><Virus><Virus-HIV><aminoacid><biophysical foundation><biophysical principles><biophysical sciences><cell culture><cohort><deep sequencing><design><designing><develop a vaccine><development of a vaccine><directed evolution><experiment><experimental research><experimental study><gp120><gp120 ENV Glycoprotein><gp120(HIV)><host response><immunogen><immunogenicity><immunoresponse><knockin><knockin mice><mAbs><mRNA><model of animal><model organism><neutralizing antibody><polypeptide><reconstitute><reconstitution><response><scaffold><scaffolding><tool><vaccine development><vaccine formulation>