P16.02
Background: Current HIV-1 vaccine strategies fail to elicit broadly neutralizing antibodies(BnAbs). Further understanding of the mechanisms of induction of BnAbs in natural HIV-1 infection will provide insights on improving the current vaccine strategies. The aim of this study is to identify samples with BnAbs activities from HIV-1 B' infected individuals and to explore potential sequence characteristics of env genes which correlate with broadly neutralizing activity.
Methods: Using a panel of 25 Env-pseudoviruses including HIV-1 clade B, C, A, CRF07_BC and CRF01_AE strains, six samples with BnAbs activities were identified from 103 samples with chronic HIV-1 B' infection. 164 env sequences were amplified by single genome amplification assay from these six samples and sequence characteristics were analyzed.
Results: Each of these six samples with BnAbs activities was able to neutralize more than 80% test strains, in which the neutralizing breadth for clade B strains is the biggest. Sequence analysis indicated the genetic diversity mainly lied in V1V2, V4, and V5 sub-regions; env genes from these samples have a longer length and more glycosylation sites at V1V2,V4 regions, but less net charge at V3 loop; preliminary sequence analysis demonstrated env genes from these samples have escape mutations in key sites of 10E8, 2G12, PGT127/128 and PG6/PG9 epitopes, and the proportion was 77.8%, 30.6%, 27.8% and 13.9% respectively. In addition, 46 specific sites and 8 co-variation patterns were identified in env genes, which may be associated with broadly neutralization activity.
Conclusions: This study demonstrated that a relatively high prevalence of BnAbs responses was detected in chronic HIV-1 B′ infection. Sequence analysis suggested that HIV-1 may escape neutralization via increasing length and the glycosylation of V1V2 and V4 loop and reducing V3 ring static charge, and different epitomes of HIV-1 env genes from samples with BnAbs activities endure varying immune pressures.
