Abstract
Background Broadly neutralizing antibodies PG9 and PG16 have been isolated from the B cells of one clade A-infected individual from IAVI Protocol G. PG16 is relatively trimer-specific whereas PG9 binds trimer preferentially, but can bind monomeric gp120 from several viral isolates. Both antibodies are potent neutralizers that recognize greater than 70% of tier 2 pseudovirues in the TZM-bl assay. We sought to begin immunogen design efforts based on sequences from the Protocol G donor, however all viruses isolated from the donor were resistant to neutralization by PG9 and PG16. We used a bioinformatics approach to infer the most recent common ancestor (MRCA) sequence for the viral envelope (Env) to identify closely related viruses sensitive to PG9/16.
Highlights
Broadly neutralizing antibodies PG9 and PG16 have been isolated from the B cells of one clade A-infected individual from IAVI Protocol G
We sought to begin immunogen design efforts based on sequences from the Protocol G donor, all viruses isolated from the donor were resistant to neutralization by PG9 and PG16
Alignment of the most recent common ancestor (MRCA) sequence with 99 subtype A gp160 sequences from the Los Alamos HIV database identified BG505 as the virus with the highest degree of homology (73%) to the MRCA sequence. Pseudoviruses prepared with this Env are sensitive to neutralization with a broad panel of bNAbs, including PG9 and PG16, indicating that BG505 has an antigen profile desirable in a vaccine candidate
Summary
Neutralizing antibodies PG9 and PG16 have been isolated from the B cells of one clade A-infected individual from IAVI Protocol G. Identification of a clade A HIV envelope immunogen from Protocol G that elicits neutralizing antibodies to tier 2 viruses S Hoffenberg1*, S Kosakovsky Pond2, A Carpov1, D Wagner1, A Wilson1, R Powell1, R Lindsay1, H Arendt1, J DeStefano1, P Poignard1, M Simek1, S Fling1, S Phogat1, C Labranche3, D Montefiori3, D Burton4, C Parks1, C King1, W Koff1, M Caulfield1
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