HIV-1 envelope proteins and V1/V2 domain scaffolds with mannose-5 to improve the magnitude and quality of protective antibody responses to HIV-1.

摘要: Two lines of investigation have highlighted the importance antibodies to V1/V2 domain gp120 in providing protection from HIV-1 infection. First, recent RV144 vaccine trial documented a correlation between non-neutralizing V2 and protection. Second, multiple broadly neutralizing monoclonal (e.g. PG9) been isolated rare infected individuals, termed elite neutralizers. Interestingly, binding both types appears depend on same cluster amino acids (positions 167–171) adjacent junction B C strands four-stranded β-sheet structure. However, mAb, PG9, additionally depends mannose-5 glycans at positions 156 160 for binding. Because immunogens used previous trials were enriched complex sialic acid-containing glycans, lacked high mannose structures required PG9-like mAbs, we wondered if these could be improved by limiting glycosylation glycans. Here, describe PG9 activity monomeric gp120s strains produced with We also properties glycopeptide scaffolds expressed The scaffold A244 isolate was able bind CH01, CH03 mAbs affinity provided that proper present. further show immunization fragments alone, or prime/boost regimen gp120, enhanced antibody response sequences associated trial.