A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors.
Pubmed ID: 27610569 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets 6X His tag?? - ChIP Grade
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis unknown targets Mouse IgG, Fc? Fragment Specific
View all literature mentionsThis unknown targets Human IgG (H+L)
View all literature mentionsThis monoclonal targets CD45R (B220)
View all literature mentionsThis monoclonal targets IgM
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD23
View all literature mentionsThis monoclonal targets IgD
View all literature mentionsThis monoclonal targets CD21/CD35
View all literature mentionsThis monoclonal targets F4/80 Antigen
View all literature mentionsThis monoclonal targets CD38
View all literature mentionsThis monoclonal targets Ig light chain lambda
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Ig light chain lambda
View all literature mentionsThis monoclonal targets IgD
View all literature mentionsThis monoclonal targets CD23
View all literature mentionsThis monoclonal targets CD21/CD35
View all literature mentionsThis monoclonal targets IgM
View all literature mentionsThis monoclonal targets CD38
View all literature mentionsThis monoclonal targets CD45R (B220)
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets F4/80 Antigen
View all literature mentionsThis polyclonal targets 6X His tag?? - ChIP Grade
View all literature mentionsThis unknown targets Human IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG, Fc? Fragment Specific
View all literature mentions