Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody

Cheng C, et al., 90(6):2740-55, J Virol., 2015

The HIV-1 envelope trimer (Env) is the main target of virus-directed neutralizing antibodies. One of the commonly used glycoprotein-mimics of HIV-1 Env is the SOSIP.664-stabilized soluble trimer from HIV-1 strain BG505. Reported in here is the enhancement of antigenic specificity of BG505 SOSIP.664 by minimizing the exposure and reactivity of the variable loop 3 (V3) region on Env. To stabilize BG505 SOSIP.664 trimer, it was coupled with the antigen-binding fragment (Fab) of broadly neutralizing antibody, PGT145. The stabilities, antigenicities, and immunogenicities of BG505 SOSIP.664 (BG505 trimer) and the PGT145-trimer complex were compared. Antigenic analysis of BG505 trimer and PGT145-trimer complex was performed by Bio-Layer Interferometry (BLI) using a Pall ForteBio Octet HTX instrument equipped with Anti-Human Fc-Capture biosensors (AHC). The binding of the ligand-free BG505 trimer and the PGT145-trimer complex to a panel of purified monoclonal antibodies (VRC01, PGT145, PGT151, F105, and 17b) were studied. Antibodies were immobilized onto AHC Biosensor probes. The sensor tips were subsequently dipped in six different concentrations of trimer. Overall results of this study reflects an improved antigenic specificity of the PGT145-trimer complex for neutralizing antibodies as compared to wild type BG505 trimer. Data also suggest that the immune response on crucial neutralization epitopes can be improved by introducing appropriate modifications to the trimer immunogens.

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